Hurrler Syndrome Case Studies

Hurrler Syndrome Case Studies
In 1981 Weissbluth et al. reported the first case of extensive MS associated with GM1 ganglio
sidosis 9. Since then some other cases have been reported linking other IEM with MS and GM1
gangliosidosis. There are 54 reported cases of extensive MS with various IEM, in which 25 cases
are associated with Hurler syndrome, 17 with GM1G, 9 in Hunter syndrome, 2 in ᶐ–mannosidosis,
and 1 with Niemann–Pick disease6. Of these 25 cases of Hurler syndrome, 19 have been reported in
a single study by Gonzalez et al8,10. However in recent years reporting of extensive MS in GM1G
is more frequent in comparison to Hurler syndrome. By 2006, only 39 cases LySD associated with
MS was reported, of these 24 patients had Hurler disease, and 11 patients had type 1 ... Show more
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Melanocyte migration and proliferation is dependent upon exogenous peptide growth factors, which
stimulate receptors with tyrosine kinase activity(Trk) . Human keratinocytes and dermal fibroblasts
express nerve growth factor (NGF), which is an important signal for transdermal melanocyte
migration. It has been postulated that accumulated metabolite like GM1 and heparan sulfate binds
tightly to Trk receptor which enhances NGF activity leading to aberrant neural crest
migration8,11.In our patient MS was "progressive" in nature, which can be attributed to activation
of latent melanocytes. It has been hypothesized that metabolite–Trk binding serves as a trigger to
dormant melanocytes resulting in progressive MS8. Treatment of GM1G is only symptomatic and
not curative. A main obstacle is blood–brain barrier, which prevents the passage of therapeutic
enzymes into the brain. Current research in animals are focused on using small molecule chaperones
to transport functional enzymes across the blood–brain barrier to slow neurologic decline but so far
without substantial success12,13. It has been seen that despite of complete normalization of white
blood cell β–galactosidase levels after allogenic BMT, patient continues to deteriorate
... Get more on HelpWriting.net ...

Hunter Syndrome Essay
Mucopolysaccharidosis Type II, also called Hunter Syndrome, is one of eleven types in a group of
rare genetic lysosomal storage disorders called Muchopolysaccharidoses or MPS. (Lorena Elena
Melit, 2015) Hunter Syndrome is named after Charles Hunter. He was a Canadian physician that, in
1917, found a rare disease in two brothers. (Lorena Elena Melit, 2015) Hunter Syndrome is the most
common of the MPS disorders. (Lorena Elena Melit, 2015) In the U.S., on average, one in every
25,000 babies will be born with some form of MPS. (Health, 2016) These disorders only affect
someone who inherits a defective gene from both parents. However, Hunter Syndrome or MPS II, is
different form the others in the group. (Health, 2016) MPS II is inherited when the ... Show more
(Health, 2016) Because patients with Hunter syndrome suffer from behavior problems, finding
solutions for this is a way to offer relief for family and caregivers. (Jane Roberts, 2016) Things that
are used are family support, behavioral strategies or a change in the patient's environment. (Jane
Roberts, 2016)Parents can make sure the patient has a safe area by using soft furniture and having
toughened glass in the windows. (Jane Roberts, 2016)Also placing the patient's bedroom and
bathroom down stairs and utilizing baby gates. (Jane Roberts, 2016) Making sure the patients
bedroom is very dark, having a sleep schedule, padding their bedroom walls and placing a mattress
on the floor will help prevent an injury. (3C) Sometimes surgery is necessary to gain relief for some
symptoms of Hunter syndrome. (Health, 2016) Patients may have their adenoids or tonsils removed
if they are suffering from spleen apnea or breathing problems. (Health, 2016) Another way to help
with the patients breathing problems is to do oxygen therapy or use a CPAP.(2) A CPAP is a
continuous positive airway pressure device that puts air into the patient's airway to keep it open
improving lung volume. (2) The patient may also need a thin tub inserted to drain fluid from their
brain if the buildup gets too high. (2) Another treatment for Hunters syndrome is Enzyme
replacement therapy. (8) It is used to reduce the progression of Hunter syndrome. (8) The earlier the
Enzyme therapy is given the more effective it will be. (3C) The Doctor uses an IV to give the patient
man made or engineered enzymes to replace the defective enzyme.

Comparison Of Lysosomes And Vacuoles
A cell is like a huge factory. Numerical amounts of processes are non–stop, even when we're asleep.
After a long day of sleeping and play, you must eat. A great meal satisfies the body; to keep moving
each and every day, but how does it get receive the nutrients and power its needs? That is through its
digestive system, but more in particular, the cell organelles. Two of these organelles work hand in
hand to keep the body functioning. The two organelles are the lysosomes and vacuoles. The two
organic like objects are like brothers. They need and depend on each other, to digest and dispose of
waste coming from the human being. These items also are located in the cytoplasm of the cell where
they are recycled and deposit fresh nutrient into ... Show more content on Helpwriting.net ...
The cell as no particular shape nor size. Vacuoles store the nutrients needed for the cell and as well
as keep it from being contaminated by the waste produced by the body. It is found in both plant and
animal cells but is much larger in the plant cell, because its main degree of function is storage of
water for the plant to larger portion of its family which is the Vacuole. It exports items outside of the
cell to keep damage to a all–time low. On the contrary, lysosomes break down food and garbage
inside the body as well. Its like the stomach of the cell. It's found in all eukaryotic cells. Lysosomes
are typically recycled back into the cytoplasm of the cell after the enzymes attack and destroy the
harmful substances that it broke down and engulfed. Lysosomes are also like the builders of the cell,
and looked upon as a reparation item. They are able to act upon this way due to a special enzyme
called hydrolytic enzymes. Enzymes within the endoplasmic reticulum plays an important role in
nurturing the process of creating a lysosome. Which information is then sent to the Golgi body and
the formation of the lysosomes are then created by the budding off of its branches and then sent to
the

Proteomics Essay
4.2 Combination of proteomics and interactomics
The study of PPI is fundamental to define the molecular networks that contribute to homeostasis of
living organisms. Disruptions in protein interaction networks have been shown to cause diseases in
both human and animals. For instance, PPI disturbances have been shown to be involved in cancer
caused by p53 mutations [47], neurodegenerative diseases resulting from protein aggregates
accumulation [48], and virus–host interactions [49]. Therefore, the monitoring and study of PPIs can
provide innovative options for identifying diagnostic and therapeutic targets that have potential for
broader clinical applicability. Technological advances in genomics and proteomics have spawned a
large number of ... Show more content on Helpwriting.net ...
Shorter routes to the clinic are also possible because in vitro and in vivo screening, chemical
optimization, toxicology, bulk manufacturing, formulation development and even early clinical
development may have already been completed and can therefore be bypassed. Collectively, these
factors enable several years, and substantial risks and costs, to be removed from the pathway to the
market [51].
By submitting the hub–bottleneck proteins identified through network analysis, we identified
potential drug repositioning candidates. Phosphoaminophosphonic acid–adenylate ester [52], is a
small molecule, classified as a purine ribonucleotide that targets HSP90AA1. It is currently
experimental and has not been evaluated in clinical trials, but is predicted to cross the blood brain
barrier. It may be a promising candidate for treating MPS VII for its anti–oxidant effects. Quercetin,
a small molecule antioxidant targeting ATP5A1, and a naturally occurring molecule, is also a
promising candidate for antioxidant therapy. It is being evaluated in several clinical trials, including
trials evaluating its use for cancer prevention, cancer treatment, and treatment of polyneuropathies.
Rifabutin, which has been shown to also be able to inhibit activation of inflammatory cells and has
demonstrated ability to target HSP90AA1, emerges as another potential drug candidate. Rifabutin is
FDA approved as an

How Do Lysosomes Cause Disease?
Lysosomes are known as the "Digestive organelle" of the cell, with their main function being to
digest intracellular components. They're characterized by a low pH and many different acidic
hydrolysis, giving them an optimum acidic environment for breaking down larger macromolecules
such as oligosaccharides and complex lipids. Once broken down, their building blocks are then
exported to the cytosol where they can be reused as nutrients in cellular metabolism. Impairment of
lysosomes to execute this process has many effects that could cause disease as well as death.
Lysosomes are able to digest macromolecules using four different processes including: Autophagy,
the digestion of intracellular components by fusing with the lysosome resulting in an
Autophagolysosome that releases the broken down components. Heterophagy, which degrades
foreign material that has entered the cell. The lysosome may self–destruct within the cytoplasm as
part of a programmed ... Show more content on Helpwriting.net ...
Similar to Niemann–Pick type C disease, Parkinson's disease demonstrates the irregular cholesterol
movement and increased levels in neurons. Parkinson's disease is the second most common
neurodegenerative disorder, effecting the motor nervous system and people's abilities to move (3).
Lysosomal storage disorders are metabolic, but however share many of the clinical features of
Parkinson's disease such as tremor, bradykinesia, rigidty and cognitive decline (3). They also have a
pathogenic overlap, both consisting of lysosomal and mitochondrial dysfunction, impaired
autophagy, alterations in lipid metabolism as well as other similar propreties (3). The similarities
between the two suggest that their encoding genes may be a carrier of a shared nucleotide variant
that could possibly be part of the cause of Lysosome storage diseases as well as the risk of
developing Parkinson's

Sanofi Genzyme: Personal Statement
As a rising junior at Tufts University earning BS in Biomedical Engineering, I am applying in the
Research and Development summer intern, and I am also interested in the Medical Affairs and
Quality Control internship at Sanofi Genzyme. Kelsey Gilchrist, a previous summer intern in the
Bone and Joint Research Group, introduced me to this fantastic opportunity. She said that she enjoys
working alongside her supervisors and seeing the impact of her work in the real–life clinical
application. I am excited about working in innovative drugs and transformative therapies, and I
really appreciate the expertise that Sanofi & Genzyme have achieved in rare diseases such as
lysosomal storage disorders, thyroid cancer and multiple sclerosis. I am passionate about the
pharmaceutical industry and I envision myself working in the field for the next 10 years. ... Show
more content on Helpwriting.net ...
I mastered not only the basic laboratory skills such as pipetting, molarity and concentration
calculations, but also the ability to maintain scientific records, and to analyze and interpret
biological and chemical products. This semester, I am taking molecular biotechnology, which will
prepare me with techniques like cell culture, in vitro/in vivo testing, and Western blotting.
Moreover, I have two laboratory experiences qualify me for a summer internship. I worked in the
inorganic battery lab in Beishida University for two years. I gained many chemistry lab skills, such
as SEM, NMR, and UV–vis spectrometer. I finished my own project on the selected–control
hydrothermal synthesis of Li battery with various cladding materials with the collaboration of my
professor and a graduate student. I have just started to work in an asthma research lab at Brigham
and Women's Hospital, where I work both in the office and on the lab bench. With the two
experiences, I am confident that I can work side–by–side with biopharmaceutical professionals and
contribute

Schindler Disease Research Paper
Have you ever felt like you were at a point in life where you stop learning and start losing what you
already know? This is what it can be like living with Schindler disease; after some months the
babies lose the skills they have learned and regress till they are completely unresponsive
(http://ghr.nlm.nih.gov/condition/schindler–disease). Schindler disease as rare as it is should receive
more help towards reaching a cure because of lifespan and prognosis,treatment(or lack of), and the
history of the disease. The lifespan for children with Schindler disease type one is very short, and
the quality of life is very bad, as to where they regress from all of the things they learned and
slipped back and forgot them and eventually become completely ... Show more content on
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Angiokeratoma corporis diffusum with glycopeptiduria due to deficient lysosomal alpha–N–
acetylgalactosaminidase activity. Clinical, morphologic, and biochemical studies. Arch Dermatol.
1993 Apr;129(4):460–5.PubMed citation Kodama K, Kobayashi H, Abe R, Ohkawara A, Yoshii N,
Yotsumoto S, Fukushige T, Nagatsuka Y, Hirabayashi Y, Kanzaki T. A new case of alpha–N–
acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Ménière's
syndrome and without mental retardation. Br J Dermatol. 2001 Feb;144(2):363–8. PubMed citation
Michalski JC, Klein A. Glycoprotein lysosomal storage disorders: alpha– and beta–mannosidosis,
fucosidosis and alpha–N–acetylgalactosaminidase deficiency. Biochim Biophys Acta. 1999 Oct
8;1455(2–3):69–84. Review. PubMed citation Sakuraba H, Matsuzawa F, Aikawa S, Doi H, Kotani
M, Nakada H, Fukushige T, Kanzaki T. Structural and immunocytochemical studies on alpha–N–
acetylgalactosaminidase deficiency (Schindler/Kanzaki disease). J Hum Genet. 2004;49(1):1–8.
Epub 2003 Dec 19. PubMed citation Umehara F, Matsumuro K, Kurono Y, Arimura K, Osame M,
Kanzaki T. Neurologic manifestations of Kanzaki disease. Neurology. 2004 May 11;62(9):1604–6.
PubMed citation rare

Essay on Tay-Sachs
Tay–Sachs
Abstract
Tay–Sachs is a disease caused by a mutation to the gene which codes for Hex A. Without Hex A, a
cell cannot degrade GM2 ganglioside into GM3 ganglioside. This results in a build up of
ganglioside's in lysosomes of neurons. The result is varying degrees of mental deterioration. New
DNA–based screening is currently being developed to replace the enzyme–based screening
techniques that have been used since 1969. This will not only speed up the diagnosis, but also allow
for earlier detection of Tay–Sachs by using the parents genotypes.
Introduction
Tay–Sachs disease is one of three autosomal recessive, lysosomal storage disorders, collectively
known as the GM2 gangliosidoses. They result from accumulation of ... Show more content on
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Hex A GalNAc–Gal–Glc–Cer –––––––––> Gal–Glc–Cer + GalNAc l l NANA NANA GM2
Ganglioside GM3 Ganglioside
Fig. 1 Shows the action of Hex A cleaving the GalNAc off of the GM2 ganglioside and converting it
to the GM3 ganglioside. This is the blocked reaction in Tay–Sachs disease. (GalNAc=N–
acetylgalactosamine; Gal=Galactose; Glc=Glucose; Cer=Ceramide; NANA=Sialic Acid ) [ 6 ]
There is also a third protein required for GM2 ganglioside hydrolysis called the GM2–activator. It
has been demonstrated that the GM2–activator extracts ganglioside GM2 from micelles or
liposomes and forms a ganglioside activator complex. This complex is required for the Hex A
enzymatic activity [ 4 ] .
The GM2–gangliosidose
There are three forms of GM2–gangliosidoses associated with either of the three gene products
necessary for GM2 hydrolysis. Tay–Sachs disease is caused by mutations in the HEXA gene which
affect the a subunit unique to Hex A. Patients with Tay––Sachs disease retain the ability to produce

Gaucher Disease Research Paper
Gaucher disease is an abnormality fat of storage. It is an increasingly genetic and very rare disorder
that is most common in family members. The people who suffer the most, have consequences in the
lack of of levels of a certain enzyme in the body. Because of this, a fatty lipid spreads throughout
one's human body. This disease is also known to be called lysosomal storage disorder. This type of
disorder can cause symptoms to happen at any time of your life, whether it is childhood or
adulthood. How can you get this disease? You can get it from parents who struggle with the cells in
their body. "The enzyme that is not working well in Gaucher disease is called glucocerebrosidase.
This enzyme helps the body break down glucocerebroside, a fatty

Niemann Pick Disease Research Paper
Niemann Pick Disease
Niemann–Pick Disease is an autosomal recessive disease, passed down through carrier parents,
where lipids gather in the cells of the spleen, liver, and brain creating an obstruction. There are four
known forms of the disease, Type A, Type B, Type C, and Type D, in which Type A and B compose
Type I and Type C and D make up Type II. Type A and B are due to a mutation in the SMPD1 gene
that causes a lack of the enzyme acid sphingomyelinase (ASM) which metabolizes sphingomyelin.
When there is an absence of sphingomyelinase the excess buildup of sphingomyelin kills multiple
cells, which leads to the stopping of organ function. The symptoms of Type A include: abdominal
swelling, redness in the eye, eating difficulties, and loss ... Show more content on Helpwriting.net ...
Due to the bodies inability to create the enzymes, the patient experiences a buildup of ganglioside
GM2, its derivative GA2, glopside, and oligosaccharides ultimately leading to the wrecking of the
central nervous system and then death. In a healthy baby, the enzyme would convert the ganglioside
into a non–toxic. The three stages of Sandhoff disease are infantile form, juvenile form, and adult
form, clearly determined by the age category in which these symptoms present themselves.
Placement of the mutation, specifically the codons on the 14 exons in the HEXB gene inscribed in
chromosome 5 of the genome, decide the form, and thus the severity of the disease. Moreover, the
infantile and juvenile form are observed to be a variation on exon 1207V pertaining to the father,
along with a 16 base pair cancellation from the mother seen in up to 5 exons. Symptoms in the
infantile form usually appear within six months of birth and the patient can be expected to die within
three years, usually from a respiratory infection. Infantile form is the most severe, while juvenile
and adult forms are rare. The symptoms that will arise during the infantile form are: loss of muscle
control and movement, hearing loss, blindness, seizures, spasticity, macrephaly, red spots in the eye,
respiratory infections, organomegaly, doll–like appearance, and myoclonus. Since it is hereditary,
each parent must be a carrier of the gene, resulting in a 25% chance that the child will inherit the
disease. The juvenile form begins with symptoms from ages three to ten, with the child living to be
around 15. Symptoms for the juvenile form include: autism, ataxia, loss of motor skills, spasticity,
and various learning disorders.

Acute Infant Tay-Sachs Disease Case Study
Pathophysiology
NEED MORE PATHOLOGY Acute Infant Tay–Sachs disease is a lysosomal storage disease
[http://www.sciencedirect.com/science/article/pii/S0925443999000745] which belongs to a group of
similarly inherited disorders that result from the defective function of a hydrolase acid. Those who
suffer from Tay–Sachs disease have a diminished level of of β–hexosaminidase A, a type of hydrolic
acid, which causes and increased accumulation of GM2 ganglioside in the lysosomal storage of the
patient. [http://hmg.oxfordjournals.org/content/11/11/1343.full] Because of the lack of β–
hexosaminidase A, the body cannot break down excess GM2 ganglioside and the fatty substance is
able to build up profusely in the nerves and tissues of the brain. ... Show more content on
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By this age, children have worstened in their lack of ability to remain attentive
[http://my.clevelandclinic.org/childrens–hospital/health–info/diseases–conditions/neurological–
conditions/hic–tay–sachs.aspx] incliding visual attentiveness, associated with the well–noted
cherry–red spot (present in all affected children) [http://www.ncbi.nlm.nih.gov/books/NBK1218/].
In children with Tay–Sachs Disease, an opthamologic test will show a positive test for a "cherry–red
spot" on the childs retina. [https://hpsrepository.asu.edu/handle/10776/2299]. In one study, 67% of
patients studied said the the initial finding of a cherry–red spot on their child lead to further testing
and therefore a diagnosis of Tay–Sachs Disease.

Inherited Metabolism
The body uses a process called metabolism to break down carbohydrates, fat and protein in food and
chemicals in the system to convert that to energy that uses. Metabolism refers to all the chemical
reactions taking place in the body to convert or use energy ("Inherited Metabolic Disorders", 2017).
Metabolism also plays a key role excretion of wastes from the body by converting excess nitrogen to
waste products, which is disposed off the body through urine. Chemicals in the body have to be
equally transformed into other substances and moved inside cells. Waste, semi finished products and
raw materials, are often used, produced, moved, and excreted. The workers on the assembly line are
enzymes and other proteins that make chemical reactions ... Show more content on Helpwriting.net
...
The diagnosis of the inherited metabolic disorders is conducted by routine testing and is normally
present at childbirth. Although this test is not conducted at childbirth many states are improving
there testing systems with use of improved technology. Thus, if the disorder is not detected at birth
may go undiagnosed until the symptoms present themselves on the patient, then a blood or DNA test
can be conducted to find out what type of disorder it is.
Treatment is quite limited for this sort of disorders because the genetic cause of the disorder can not
be corrected but this treatment that can help the patient such as reducing the intake of food or
medicines that can not be effectively metabolized. By replacing the enzyme or other chemical that is
missing or inactive, to restore metabolism to as close to normal as possible is helpful ("Inherited
Metabolic Disorders", 2017). Special diets, detoxifying blood and enzyme replacements.
Reference
Inherited Metabolic Disorders: Types, Causes, Symptoms, and Treatments: WebMD. (2017).
Retrieved from June 24, 2017, from http://www.webmd.com/a–to–z–guides/inherited–metabolic–
disorder–types–and–treatments#1 Neurology. (n.d.). In Wikipedia. Retrieved August 8, 2007, from
http://en.wikipedia.org

Taking a Look in Tay-Sachs Disease
The cell is the basic unit of life in eukaryotic organisms. The inside of the cell is comprised of
multiple subunits called organelle that all function together to maintain homeostasis and function.
Each individual organelle is assigned a specific task and purpose for the cell. These tasks and
purposes can range from structural support all the way to the disposal of malfunctioning organelle.1
Similarity to a machine, if one part stops functioning to full potential, serious if not fatal
consequences can be faced. A shining example of the effects of a malfunctioning organelle occurs in
Tay–Sachs disease. Tay– Sachs disease is a lysosomal disorder that is caused by a faulty lysosome.1
Recent studies and research have been investigating the causes and pathways Tay–Sachs disease
with great success, which is amazing news for the scientific community.
Lysosomes are membranous sacs of enzymes that are typically are involved in the digestion of
cellular macromolecules. They are made by both the endoplasmic reticulum and the Golgi complex.
Lysosomes have various roles, including the recycling of the cell's organic material and in the
intracellular digestion of macromolecules. The digestion of macromolecules is carried out through
an intense concentration of enzymes. To be specific, lysosomes contain close to 50 different
degrading enzymes that are capable of hydrolyzing proteins, DNA, RNA, polysaccharides, and
lipids within the cell.1 All of lysosomal enzymes are acid hydrolases,

Anderson Fabry Disease: A Case Study
A five year old male child was admitted to the ER on complaints of burning sensations in his hands.
Further examination on the child discovered that he had many inflamed spots (angiokeratomas) on
his upper legs. The child's paternal grandparents including his father are all normal. The child's
maternal grandfather had angiokeratomas and died at the age of 45 due to kidney and heart disease,
while his maternal grandmother was normal. The five year old's mother had some angiokeratomas.
The patient is diagnosed with the rare Fabry disease also referred to as Anderson–Fabry disease.
Anderson–Fabry is an X linked genetic disease. It is a lysosomal storage disorder that is passed
through genes and must be inherited as it runs in relatives. Since

The Normal Cellular Location Of The Crusoe1
Assignment – Michael Layland – C1476301 – I1417
Q1: What does the comparison of the supernatant fraction between the experimental and control
samples prove, regarding the normal cellular location of the CRUSOE1? [2 marks]
A1: Triton X–100 is a detergent in laboratory practice and is used to permeabalize unfixed
eukaryotic cell membranes and aids in solubilizing membranous proteins. The addition of the
substance Triton X–100 would cause the majority of the cell membranes to become permeable thus
allowing contents of the eukaryotic cell to leave via simple diffusion hence the large concentration
of radioactive prominence to be situated in the supernatant fraction. Again, the detergent property of
Triton X–100 is further reinforced by the fact that it causes the majority of all radioactive sulphur to
be situated in the supernatant. Without the addition of Triton X–100 the graph displays the greatest
quantity of radioactive sulphur to be situated in fraction 3 of which a majority of "small organelles"
are situated ranging from a diameter 0.2 to 1.5 μm. It is due to this fact that one can assume the
normal cellular location of the CRUSOE1 protein to be situated in normal cellular location in
organelles of the previously stated diameter and not it the cytoplasmic structure as the addition of
Triton X–100 would assume.
Q2: Professor Holton's team speculate that CRUSOE1 is located predominantly in the Lysosomes of
the cell. Is this a reasonable assumption to make, and why? [4

Single Gene Disorder
When a certain gene is known to cause a disease, it is referred as a single gene disorder or a
Mendelian disorder. These disorders involve mutations in the DNA sequences of single genes. As a
result, the protein the gene codes for is either altered or missing (Landsverk, 2013). Few examples
of single gene disorders includes cystic fibrosis, sickle cell disease, Fragile X syndrome, muscular
dystrophy, or Huntington disease. As a rule, single gene disorders are not very common. For
example, only one in 2,500 people are born with cystic fibrosis. There are a number of inheritance
patterns of single gene disorders that are predictable when you know what they are. There are three
main transmission patterns: autosomal–dominant, autosomal–recessive, and X–linked or sex–linked
recessive (Mahdieh, 2013). ... Show more content on Helpwriting.net ...
LSDs result from incompletely digested macromolecules due to loss of enzyme function (Filocamo,
2013). These enzymes normally break down items for reuse in the cells. If the enzymes are missing
or don't work properly, then the items can build up and become toxic. This happens in an area of the
cell called lysosomes. To date, 51 genetically determined lysosomal storage diseases have been
described. Since there can be different mutations of the same gene, they result in different clinical
manifestations and are classified as infantile and adult types. The acquired disorders are the result of
inhibition of α–mannosidase II by ingestion of plant materials of Astragalus lentginous, Oxiftropis
serica, Swainsona canescens, and Ipomoea carena as well as treatment with certain drugs, such as
amphophilic cationic drugs, amiodarone and chloroquine, which induce phospholipidosis and MPS.
There are 9 different inherited and 2 acquired mechanisms that are known to cause lysosomal
storage

A Short Film 'Hardships Of Disability'
Short Film Examines the Hardships of Disability
Adam New
Imagine is a brief and melancholy exploration into the lives of a family that is forced to deal with a
rare genetic disease.
Here in the year 2017, we are very fortunate to be living at a time of medical advancement. Ailments
and illnesses once thought to be death sentences centuries or even decades ago can be cured by a
simple pill or vaccine. With that said, scientists and doctors still do not have all the answers. While
we are much less likely to die of common diseases, there are some that are not so easily combatted.
Some afflictions are difficult or near–impossible to treat, and this is especially arduous for those
who are born with them. People suffering from genetic diseases ... Show more content on
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As the child grows up dealing with the complications of the illness, her mother (Claire Whitelock)
and father (Dan Burman) try to cope with the fact that their daughter cannot have a normal life.
Given his age, Mason's skills as a director shine brightly in this piece. The cinematography, editing,
lighting, and acting are all top notch. This young man has some serious talent, and has a lot of
potential going forward as a filmmaker. If you want to cry at a short film, Imagine will fulfill that
need. This dramatic short will make you commiserate with the characters, and hope against all hope
that Millie gets better. Parents can relate to the heartache of seeing their children go through so
much pain, and when the family in the film react to their daughter's condition, it comes off as
genuine. Imagine is unrelenting with its melancholy tone. There are no jokes to bring levity to the
situation. There is no sugarcoating of the deadly circumstances that Millie is forced to confront.
While this does make the short film hard to sit through, it brings an air of realism to the story.
Families dealing with NP–C know how serious the condition can be, and know that it is no laughing
matter. It also emphasizes the need for funding the research of this disease, which is why it was
made in cooperation with several charities dedicated to the fight against it. Imagine may not be the
most uplifting of tales about fighting disease, but it is a much needed look into the lives of those
who are affected by

Gaucher Disease Types I, II, IIi
Gaucher Disease Types I, II, III
Gaucher Disease is a type of lysosomal storage disorder. The importance is that they are meant to
keep everything in order. Lysosomes are microscopic organelles that have a primary function to
serve as digestion compartments. According to Davidson, (1) "lysosomes help break down many
different materials such as fats, proteins, waste products, and more to transfer those compounds to
become new cell building materials". Consequentially, making lysosomes an important factor to our
daily functions in life. Lysosomal storage diseases form due to the modification of lysosomal
enzymes. The diseases can be metabolically inherited through gene mutation. In "Lysosomal Storage
Disease", Michael Kruer (2) claims that, ... Show more content on Helpwriting.net ...
In fact type two and three effect the brain and spinal cord becoming very serious. In contrast, Type
three is not as quick to become evident in young children. Similar to type one, type three can show
up later in childhood, and take longer to progress into worse symptoms. Sadly, infants that are
proscribed with type two disease normally don't live to see the age of three. Type two disease
quickly takes effect over a person, not allowing the chance for growth into adulthood. The most
severe Gaucher's disease is Perinatal lethal, which can kill an infant in a matter of days after being
born. The causes for Perinatal lethal, according to Web MD (3) are, "too much fluid in baby's body
before or after being born, dry skin, enlarged liver and spleen, and severe brain and spinal cord
problems." Because of these problems an infant will not be capable of having much of a chance to
grow and mature, due to the weakness of being a fragile newborn.
Ages that symptoms begin, normally vary due to what type of disorder the person has. The main
problem with lysosome diseases are that they are genetically inherited. Which means, that mothers
and fathers genetically carry some type of disorder and pass it down to their children. Because of
this being caused by genetics, symptoms will normally begin based upon what type of disorder that
is inherited. Which makes it hard to know at what age symptoms will

Symptoms And Symptoms Of Mcardle 's Syndrome
McArdle 's Syndrome is a muscle metabolism disorder that is caused by a deficiency of the
glycogen enzyme muscle phosphorylase (Quinlivan). Muscle phosphorylase is the enzyme that
breaks down glycogen during glycolysis. Without this enzyme, the body has a difficult time going
through anaerobic glycolysis and can cause an individual to experience intense muscle pains. It is
estimated that 1 in every 100,000 people will get McArdle 's Syndrome (Haller). McArdle 's
Syndrome is a genetic disorder, so there is no preventing it. Even the unaffected child of an affected
person will have a 50% chance of being a carrier, which means they could pass it on to their own
children (Martín). Other common names for McArdle 's Syndrome are Glycogen Storage disease
type V (GSDV) and McArdle disease (Martín, Quinlivan).
The symptoms of McArdle 's Syndrome were recognized about 65 years ago by Brian McArdle. In
1959, it was found that all these symptoms were due to a glycogen phosphorylase deficiency in the
muscles (Haller). Some of these symptoms include rapid fatigue, myalgia, and muscle cramps in
exercising muscles. These symptoms usually occur during the first 10 minutes of exercise. Muscle
cramps are one of the major signs of McArdle 's Syndrome. To prevent these muscle cramps, one
should avoid high intensity and maximal aerobic exercise. Muscle weakness occurs in 25% of
people diagnosed with McArdle 's Syndrome and is more likely to involve proximal muscles and
people over the age of 40.

Lysosomal Porage Diseases Case Study
ABSTRACT
Lysosomal storage diseases (LSDs) are a group of genetic disorders, resulting from deficiencies of
lysosomal enzyme. Genotype–phenotype correlation is essential for timely and proper treatment
allocation. Recently, by integrating prediction outcomes of 7 bioinformatics tools, we developed a
SAAMP algorithm to predict amino acid substitutions. To optimize this approach, we evaluated the
performance of these bioinformatics tools in a broad array of genes. PolyPhen and PROVEAN had
the best performances, while SNP&GOs, PANTHER and I–Mutant had the worst performances.
Therefore, SAAMP 2.0 was developed by excluding 3 tools with worst performance, yielding a
sensitivity of 94% and a specificity of 90%. To generalize the guideline to ... Show more content on
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It depends on the degree of protein function affected by specific mutations, the biochemistry of the
storage materials, as well as the cell types where storage occurs.
Diagnosis of LSDs is an often long and burdensome odyssey [4], which usually includes
quantification of macromolecules excreted in urine, enzyme assay with leukocytes (or cultured skin
fibroblasts), mutation analysis and symptoms–based judgment. An alternative approach is newborn
screening (NBS) program, which shortens the diagnostic process. Early detection by NBS allows for
early initiation of disease modifying treatment which is essential for optimal treatment efficacy.
However, NBS usually leads to the identification of individuals with low enzyme activity with
previously unreported genetic variants of unknown significance [5]. Therefore, decisions on
treatment initiation can be complicated in pre–symptomatic patients, and a robust phenotypic
prediction is essential.
To this end, we utilized the bioinformatics tools to analyze mutations in the IDUA gene and
established a guideline for predicting genotype–phenotype correlation [6]. As shown in Figure 1, a
step–by–step guideline for phenotype prediction of MPS I disease was established. When a mutation
is identified, 1) if it is a known disease–causing mutation, refer to previous literature for deducing
phenotype severity; 2) if not, conduct in silico analyses. More

Case Study On Stress Management
FACULTY OF HEALTH AND ENVIROMENTAL SCIENCES
DEPARTMENT OF CLINICAL SCIENCES
PROGRAMME: EMERGENCY MEDICAL CARE
MEDICAL CASE STUDY
STRESS
Compiled by:
Rodney W.K Heyns
213098814
CONTENT
TOPIC PAGE No:
Introduction 3
Stress 3
Types of stress ` 3
Psychology behind stress 4
Specific Case Discussion 4
Dispatch Information 4
Differential Diagnosis 5
History Taking 7
Assessment 8
Emergency Management 9
Progress & Prognosis 9
Clinical Reflection on Case 10
Personal Assessment 11
Conclusion 12

Reference List 12
Annexure A (Patient Report Form) 13
INTRODUCTION
The human body relies on stress to get most of our daily ... Show more content on Helpwriting.net
...
Treat the complication that the patient presented with, which was pain management.
Action Initiation of Intravenous access for subsequent pharmacological management at the hospital
Re–evaluate our actions to see whether our interventions were effective. Make the patient
comfortable on our stretcher to relieve some of the uncomfortability.
Evaluate Outcomes Intravenous access attempts were successful patient still did not regain
consciousness and was transported to hospital in her current state.
Reflection & New Learning Our management for this patient was competent and given the
circumstances we could not do more for the patient. I learned that I learned that hypoglycaemia can
also be secondary to psychological problems and the patient presents exactly the same as for a
patient in a hypoglycemic state. Once again it is proven that each and every patient is unique and
should be treated according to their clinical presentation and not as per how another patient
presented in a similar condition. Treat the patient individually and as he/she clinically presents.
TOTAL WORDS ON CLINICAL REASONING: 583
PERSONAL

Abnormal Intracellular Zinc Metabolism Caused By...
Abnormal Intracellular Zinc Metabolism Caused by Disruption of the TRPL1–TMEM163 Protein
Interaction
Keywords: Zinc, TRP ion channel, Lysosomes, TMEM163, MLIV
Mucolipidosis type IV (MLIV) is a human lysosomal storage disorder characterized early in life by
neurodegeneration, visual impairment, low muscle tone, and impaired secretion of gastric acid1.
MLIV is caused by loss–of–function mutations or deletions in the Mucolipin–1 gene2 resulting in
the absence or a dysfunctional protein product called transient receptor potential mucolipin–1
(TRPML1) ion channel. TRPML1 consists of six predicted transmembrane (TM) domains with
channel features showing inward rectification, and non–selective permeability to calcium (Ca2+),
zinc (Zn2+), iron (Fe2+), and manganese (Mn2+) 3. Some of the cellular phenotypic characteristics
of TRPML1 dysfunction include hyperacidic lysosomes, lysosomal swelling, and lipid
accumulation. More recently, irregular levels of specific trace metals have been suggested to
contribute to the abnormal cellular phenotype, as well as the progressive cell degeneration
associated with TRPML1 dysfunction4.
The permeability of Zn2+ to TRPML1 suggests that this ion channel may play a role in Zn2+
regulation. A recent investigation of cytoplasmic Zn2+ accumulation in TRPML1 dysfunctional
cells suggests the possibility that this protein may normally function to transfer Zn2+ from the
lysosome to the cytoplasm5. Other studies suggest a significant increase of Zn2+ in the

The Complex And Major Organ Of Our Body Perform Essay
Kidney
It is a complex and major organ of our body perform several important functions like formation of
urine, water and salt metabolism, acid–base balance, regulation of blood calcium level and secretion
of hormones (Padmalochana et al.2015). The kidney is composed of many tortuous, closely packed
uriniferous tubules, bounded by a delicate connective tissue in which run blood vessels, lymphatics
and nerves. Each tubule consists of two embryologically distinct parts, the nephron, which produces
urine, and the collecting duct, which completes the concentration of urine and through which urine
passes out into the calyces of the kidney, the renal pelvis, the ureter and urinary bladder. A renal, or
uriniferous, tubule consists of a glomerular capsule that leads into a proximal convoluted tubule,
connected to the capsule by a short neck and continuing into a sinuous or coiled convoluted part .
This straightens as it approaches the medulla, and becomes the descending thick limb of the loop of
Henle, and then the ascending limb by an abrupt U–turn. The limbs of the loop of Henle are
narrower and thin–walled within the deeper medullary tissue, where they become the descending
and ascending thin segments. The ascending thick limb continues into the distal tubule. The tubule
wall shows a focal thickening, the macula densa, where it comes close to the vascular pole of its
parent glomerulus at the start of the convoluted part of the distal tubule. The nephron finally
straightens once

The Causes Of Lysosomal Diseases
More dysregulated metabolites were identified in the liver (n=177) than that in the brain (n=122).
Notably, there are more amino acid, amino acid derivatives and dipeptides identified in livers
(mostly upregulated). These results are expected because the liver is the primary site of metabolism.
In terms of pathways enriched, significant involvement of neurotransmission and chemical synaptic
transmission were observed in the brain. Meanwhile, there are several pathways only enriched in
livers, including gamma glutamyl cycle, leukotriene biosynthesis, Phase II conjugation and
glutathione synthesis, which are mainly associated with oxidative stress and inflammation. The
energy imbalance in SD leads to increased respiratory chain activity in ... Show more content on
Helpwriting.net ...
The oxidative stress can cause cell damage, resulting in inflammation, which has also been found to
be a major contributor to disease progression of GM2 gangliosidosis [17]. In this study, we
identified elevation in glutathione pathways, which plays a pivotal role in responses to oxidative
stress. Another evidence of inflammation is reduced levels of arachidonic acid, an omega–6 fatty
acid, in brain samples of SD mice. Oxidation of arachidonic acid can generate leukotrienes, a family
of eicosanoid inflammatory mediators produced in leukocytes, and thus promote inflammation. The
increased energy requirements can also activate autophagy and protein catabolism, which have been
found in MPS I and MPS VII mice [13]. In this study, we found increased levels of amino acids,
amino acid derivatives and dipeptides, indicating increased protein catabolism. Increased
requirements of energy and raw materials can also activate lipid metabolism and carbohydrate
metabolism, manifested by decreased adiposity, a common observation in many lysosomal diseases
[18–20]. In addition, the enlarged lysosome and distended cells due to abnormal accumulation
requires increased membrane synthesis, which can also affect lipid metabolism. Our previous
proteomic analysis [21] also identified abnormality in the cytoskeleton system, which can be
partially attributed to altered cellular architecture due to storage accumulation. Collectively, we
show here that the energy imbalance caused by the lack of

Restrictive Cardiomyopathy Essay
Other forms of secondary restrictive cardiomyopathy include scleroderma, Friedreich's Ataxia,
hemochromatosis, glycogen storage disease and sarcoidosis. Chemotherapy and radiation therapy
used to treat cancer can also cause restrictive cardiomyopathy. Sarcoidosis is caused by the
infiltration of granulomas in the heart and other tissues of the body. Lungs and lymph nodes are the
main organs targeted by this disease, but no organ is spared as it also affects the central nervous
system and skin. In the USA, the occurrence in the white population is estimated to be 11 per
100,000. It affects people between the ages of 20 to 30 years and occurs more in women than in men
(Dubrey, Bell, Mittal, 2007). Hemochromatosis is caused by the buildup of iron in the heart tissue
which can then lead to heart arrhythmias. Scleroderma is a disorder of the connective tissue that
leads to fibrosis of the skin, heart and lungs. Glycogen storage disease, also named Pompe's affects
infants. It causes increased storage of glycogen and fat tissue in the body. This causes the heart then
to become very heavy and thick. Infants tend to struggle to breath, have trouble feeding and fail to
meet developmental steps on time like rolling over and sitting up. Fabry Disease, a glycogen storage
disease, is an ... Show more content on Helpwriting.net ...
Kussmaul's sign can be observed due to increased venous pressure. Heart sounds are usually normal,
however a third heart sound referred to as S3 may be heard due to rapid ventricular filling.
Regurgitation murmurs may also be heard. EKG abnormalities vary depending on the progression of
the disease, but are abnormal in more than 90% of cases (Reardon 2017). Abnormalities include a
low voltage QRS most often due to an infiltrative disease, atrial arrhythmias and abnormal ST–T
waves. Chest radiography shows a normal cardiac profile with cardiomegaly and bi–atrial
enlargement. Pleural effusions may be present as

Gaucher Disease Essay
Gaucher disease (GD) is an autosomal recessive inborn error in the pathway of sphingolipid
catabolism. Biochemically, this disease is characterized by a deficiency of lysosomal β–glucosidase
(glucocerebrosidase GCase, E.C.3.2.1.45) enzyme due to the mutation of GBA gene [1]. The natural
substrate of this lysosomal enzyme is glucocerebroside (also called glycosylceramide) mainly
present on the cytoplasmic face of cellular membranes and on the cell surface. Lysosomal β–
glucosidases play a key role in recycling of this substrate by degradation of glucospingolipid from
membranes of apoptatic white blood cells and senescent red blood cells. Genetic mutations of GBA
gene affect the enzyme`s catalytic activity and stability and results in the storage ... Show more
Rarely the mutation of PSAP gene that encodes activator protein saposin C (enhances the activity of
GCase) may cause gaucher disease [3–4]. Gaucher disease can be classified into three types
depending on the presence or absence of neurological features Type I GD1– adult or visceral form is
characterized by the lack of central nervous system (CNS) involvement and accounts for almost
95% of GD; Type II GD2– infantile progressive neuropathic form with a life expectancy of <2
years; Type III GD (GD3) – juvenile, subacute neuropathic form [5]. Pathologically, patients with
the adult non– neuropathic form of the disease have deposition of glucocerebroside in lysosomes of
reticuloendothelial cells, particularly in the spleen, bone marrow and liver and frequently there is
hepatosplenomegaly, anemia, and thrombocytopenia. It has been suggested that these tissue
abnormalities in some gaucher patients may trigger macrophage activation and could result in
enhanced inflammatory agents secretion and had increased levels of pro–inflammatory (i.e., TNF α,
IL–6, IL–8, and IL–1b) and anti–inflammatory cytokines (i.e., CD14) in serum and/ or tissues

Use of Energy by the Human Body
Throughout a normal day, the body uses glucose in the form of energy. The glucose that the body
uses is attained from carbohydrates that one receives from a meal eaten during the day. However,
when glucose begins to run out, especially if a person is rigorously exercising, and is not
"restocked," the body must use its energy supplies, glycogen. Glycogen is one of the most important
polysaccharides in the human body. It is the body's stored energy; with the highest storing sites
being the muscles and liver. Glycogen is important to the liver because it is able to provide a backup
supply of glucose so that blood glucose concentration is maintained at a sufficient level to supply
the brain during times of starvation. Glycogen's function in sustaining blood–glucose levels is
imperative because glucose is essentially the only fuel source used by the brain. The primary
function of muscle glycogen is to supply fuel for the contraction of the muscles during exercise.
However, insufficient amount of glycogen in the liver and muscles can lead to numerous diseases,
diseases like Glycogen Storage Disorders (GSD). Glycogen synthesis and breakdown occur by
distinctive pathways that are catalyzed by different enzymes. Glycogen phosphorylation involves
three steps: the first is the release of glucose 1–phosphate from glycogen, then altering of the
glycogen substrate to allow additional phosphorylation, and last is the conversion of glucose 1–
phosphate to glucose 6–phosphate. Glycogen

Factors That Affect The Human Body
The term lipid refers to a broad category of molecules, which serve a wide range of purposes in
nature. Lipids tend to be hydrophobic in nature but there are also lipids that are amphiphilic as well.
It is this characteristic that allows these group of structures to serve a range of functions. In the
human body there some important lipids include glycerolipids, glycerophospholipids, and sterols,
and sphingolipids. Glycolipids are important as they serve as the body's way of storing energy.
Glycerphospholipids are important as they make up the structure of cell membranes.1 Sterols are
important because they are necessary for membrane rigidity and used as hormones and means of
signaling in the body. Sphingolipids, particularly Sphingomyelin are another group of lipids that
serve an important part of cells structure as they are found in plasma membranes of myelin sheaths.1
With this in mind, lipids are regulated and errors in the mechanism of storage and degradation can
have a negative effect on the body. Various pathways that help build, store and breakdown the
different lipids are regulated through enzymatic activity. When these enzymes are altered or
deficient, various problems can develop and lead to serious diseases. Lysosomal Storage Diseases
are one of the main disease states associated with lipid storage malfunctions, as there are various
enzymes that are involved in lysosomal degradation pathway.1 In this specific pathway, the loss of
function through mutation or

Niemann: Pick's Disease Essay
Niemann: Pick's Disease
Niemann Pick disease consists of a group of genetic disorders in which the common feature is a
varying degree of sphingomyelin storage in certain tissues of the body. According to the current
classification based on the enzymatic defect underlying these disorders, two main groups are
distinguished. The first group, which comprises type A, which is characterized by a severe
deficiency in acid sphingomyelinase activity, includes infantile neuronopathic form; and type B, an
adult chronic form without neurologic symptoms. In the second heterogeneous group called type C,
neuro–visceral involvement is massive and lipid metabolism is affected.
The sphingomyelin that accumulates in the lysosomes of the ... Show more content on
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The reason for this significant difference in neurological involvement is not clear, but it may be
consistent with the level of residual sphingomyelinase activity. Fibroblasts from normal individuals
and patients with Niemann– Picks disease types A and B, synthesize the sphingomyelinase
polypeptide having the same molecular mass 110 Kilo Daltons (KDa) and in the same degree of
abundance, during further processing the 110 KDa polypeptide is processed to a lower molecular
weight 84 KDa. Deficiency of sphingomyelinase is due to intragenic defects. Experiments done so
far, suggest that specific defects could be small inframe deletions or additions or point mutations.
The differences in clinical course of types A and B suggest that mutations are different.
Sphingomyelinase follows the same intracellular targeting and post–translational processes as the
majority of the lysosomal hydrolases. However, unlike any other enzyme there are two differently
sized polypeptides which are differentially distributed in tissues. In tissues like brain the smaller
polypeptide (molecular weight = 80 KDa) is found, whereas kidney contains both the polypeptides
(110 and 80 KDa). There is no precise explanation for the occurrence of single differently sized
polypeptides in some tissues, and the presence of both forms in tissues

Tay-Sachs Syndrome
Some of the general symptoms of the disease can be characterized by hind limb spasticity, weight
loss, tremors, abnormal posture with lordosis, and possibility of visual impairment. Muscle
weakness, clasping of the limbs, and myoclonic twitches of the head that can be onset late in the
disease. Research of the GM2 ganglioside has revealed that storage of the fatty substance varies a
large
Tay–Sachs Disease2 amount in different regions, but the majority resides in the pyriform cortex,
hippocampus (CA3 field, subiculum), amygdala, hypothalamus (paraventricular supraoptic,
ventromedial and arcuate nuclei, and mammillary body), and the somatosensory cortex (layer V).
Most symptoms of the disease often display the first signs of the disease at ... Show more content on
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There are multiple treatment options including medication, respiratory care, feeding tubes and
physical therapy. Some medications are available and can help with seizures. Both respiratory care
and feeding tubes help to avoid infections of the lungs. Breathing problems and mucus build up are
common symptoms of Tay Sachs. Physical therapy is very
Tay–Sachs Disease3 effective at keeping movement within the joints possible and helps to relieve
stiffness of the patients ("Tay–Sachs disease", 2016). There are a few experimental treatments
developing. The first is Tay–Sachs Gene Therapy, this treatment includes introducing genes into
diseased cells to try and correcting the mutations such as lysosomal defects (Cachon–Gonzlez, et al.,
"226. Effective Gene Therapy in an Authentic Mouse Model of Tay–Sachs Related Diseases",
2006). Cross correction mechanism is the proposed mechanism of action.
Social, Political, Economic

Indications For Liver Biopsy And Histological Assessment...
INDICATIONS FOR LIVER BIOPSY
Liver biopsy and histological assessment of the liver has now taken on an important role in clinical
management. Therefore liver biopsy currently has two major roles:
(A) Diagnostic purposes: Liver biopsy is helpful in diagnosis of many forms of liver disease such as
acute and chronic hepatitis (Wilson disease, alpha–1–antitrypsin disease, glycogen storage diseases,
AIH, NiemannPick disease and others), cholestatic disorders, fatty liver disease, vascular diseases,
inﬁltrative or storage diseases, some infectious diseases, and other disorders that may be associated
with characteristic histological abnormalities. It also plays a role in the diagnosis of patients with
abnormal liver tests of unknown etiology (Czaja et al., 2007). (B) Liver biopsy in the assessment of
known liver disease: Liver histology is also commonly used in disease monitoring of patients with
AIH. First, the portal–based plasma cell inﬁltrate may predict relapse and second, liver biopsy is
often obtained prior to steroid dose reduction and/or discontinuation of immunosuppressive therapy
(Rockey et al., 2009). 1– Neonatal Cholestasis Some forms of neonatal cholestasis can be identified
biochemically and genetically, but others require LB.
Biliary atresia (BA): Typically neonates with BA have acholic stools, firm livers, and abnormal
values for biochemical markers of hepatobiliary injury. Histopathologic evaluation permits
diagnosis of BA in 96% of adequate LB

A Study On A Fourth Month Male Child Essay
Introduction
The case study focuses on a 15th month male child (proband) brought by his mother to a
pediatrician with inconsolable crying due to acroparathesia in the lower extremities and
angiokeratomas on his skin. The mother is 30–year–old Japanese healthy female (consultand) with a
history of hypohydrosis. The proband has two siblings, a 6–year–old sister with a mild hearing
deficit in both ears and a 4–year–old sister with no medical history. The consultand has two siblings,
a 34–year–old healthy male with a history of hypohydrosis and 19–year–old sister with
angiokeratomas similar to the proband. The consultand's father and uncles have passed away at
young ages ranging from 42– 50 due to acute myocardial infarction, renal failure or acute stroke.
The proband's father is Caucasian with a history of mild hypertension. The paternal grandparents
have a medical history of mild hypertension (paternal grandmother) and hypocholesteremia
(grandfather). Overall, the medical and family history of the proband is consistent with X–linked
disease known as Anderson–Fabry disease as the affected male (consulstand's father) passed his X
chromosome to all of his daughters (consultand and sister). In this way, all daughters of affected
males will have the gene for Anderson–Fabry disease.
What is Anderson–Fabry disease?
Anderson–Fabry disease, commonly known as Fabry's disease is an X linked lysosomal storage
disorder, specifically a deficiency in lysosomal enzyme alpha–galactosidase A

The Effect Of Glycogen On A Healthy Body
Glycogen is a carbohydrate and mainly a stored form of glucose. This assignment will also include
the molecular structure of glycogen. This molecular glycogenic structure (diagram) will be
embedded into the body of the essay, together with the explanation of this molecular structure.
Specific reference will be made to the polisaccharide characteristics thereof and will indicate the
relation between different sub–divisions of the structure and how, where and why they are bonded
together. The function of glycogen will be discussed and the impact of glycogen on a healthy life
will be explained. Finally, the complications associated with a glycogen imbalance in the body, with
specific reference to Glycogen Storage Disease (GSD) Type I and Type II, and the impact on a
healthy body will be discussed.
Glycogen is a multi–branched polysaccharide and is utilized as energy storage. Glycogen is a
polymer of α –glucose and is often referred to as 'animal starch' as it is the principal storage
carbohydrate in animals. Glycogen is found in the liver and skeletal muscle. Its molecular structure
is very similar to that of amylopectin shown herewith, but with many more 1–6 α branches. Most of
the glucose residues in glycogen are linked by α 1,4–glycosidic bonds. With most branches,
approximately every tenth residue is created by α 1,6–glycosidic bond. The molecular formula for
Glycogen is C24H42O21. Retrieved from: http://fashions–cloud.com/pages/m/molecular–structure–
of–glycogen/
In

Tay Sachs Disease In Children
Imagine giving birth to a beautiful seemingly healthy baby, the doctor wiping him or her off and
handing it to you. Two days later, the hospital discharges you, and you begin to spend the next 3
months adjusting your new baby to your home. Towards the 4 month mark you realize some serious
symptoms that are hard to ignore such as the inability to grow beyond his or her small figure.,
inability to hold something like a spoon or even your finger,and lastly lack of eye contact. Scary as
this scenario may seem, at least 16 babies are diagnosed with Tay–Sachs disease in United States
every year. Unfortunately, the diagnosed cases are only found in toddlers because, children with this
disease only survive to the age of 5 years of age.
Tay–Sachs ... Show more content on Helpwriting.net ...
Because of this discovery, techniques to find and diagnose ineffective enzymes were developed.
These tests are extremely expensive but very effective as long as the the pinpoint of the exact
mutation can be found. Over the years, DNA–based tests have advanced so much that some doctors
can detect early symptoms even in the womb. Unfortunately there is not cure for Tay Sachs disease
nor a sure way to prevent it, but only ways to make the child more comfortable. Scientists
recommend genetic DNA testing early on to determine whether it is genetic within the family or if
something has gone wrong within the mother, so that the mother can better prepare for the

Pompe Disease: A Case Study
Pompe disease or lysosomal disorder in which it is referenced contains an acid alpha glucosidase
(GAA) that is sometimes deficient or absent in the body. Similarly, if there is an absence of acid
maltase it will lead to an excessive buildup of glycogen in lysosome derived vacuoles. The existence
of abnormal quantities of glycogen disturbs the normal design and function of the affected cells and
the excess glycogen is found in the vacuolar system. Thus, when there is a deficiency of the
lysosomal enzyme it results in the developing expansion of glycogen filled lysosomes which occurs
in several tissues like the cardiac and skeletal muscle, two of which has been affected the most.
Glycogen is a polysaccharide and is the primary storage form of ... Show more content on
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Clinical indicators depend significantly on the levels of residual enzyme activity. The most severe
form of Pompe disease is known as the classic infantile that often occurs within the first months of
life, this is described profound muscle weakness the hypertrophic cardiomyopathy, and skeletal
muscle myopathy. One of the leading indicators of Pompe disease in infants that can be detected by
chest X–rays is the massive cardiomegaly. Infants generally demonstrate signs of diminished
ventilation and constant infections as a result of weak respiratory muscle and cardiomegaly. Infantile
acid maltase deficiency is a perfect example of a motor neuron and metabolic myopathy that results
in hypotonia. Consequently, is the most severe and worse prognosis with death ranging between the
ages of 6 months and 2 years. Typically, many patients do not survive beyond the first year of life
and die as a result of heart failure. Similarly, there have been clinical presentations on infants that
had less severe cardiomyopathy; absence of left ventricular outflow obstruction and an extended
survival rate have been categorized as a non– classical infantile

The Batten Disease And Its Effects On The Nervous System
Neuroscience 4100
Kristen Miller
Extra Credit Paper
Batten Disease
The Batten disease is characterized as an autosomal recessive, fatal disorder that consists of
detrimental effects on the nervous system. Although the disease typically presents during childhood,
there are many forms that show signs at various ages. Batten disease, also known as Spielmeyer–
Vogt–Sjögren–Batten disease, is named after the British pediatrician who first correlated its
symptoms with the disease progression in 1903. This disease is the most common type of a group of
disorders called neuronal ceroid lipofuscinoses, or NCLs. Although Batten disease originally
referred specifically to the juvenile form of NCL (JNCL), the term is now increasingly used by
pediatricians to describe all forms of NCL.
There are four main types of NCL: infantile, late infantile, juvenile and adult. The signs and
symptoms of these forms are extremely similar, with the main difference being the age at which the
disease presents.
Juvenile NCL is classified as the original Batten disease because it is the most common form of the
disorder and progresses less rapidly than other types. First symptoms of this progressive disease
typically begin to develop between the ages of four and seven, when a previously normal child
develops vision complications or seizures (Pearce, 2007). Although, in other cases, changes may be
more minor and manifest in behavioral changes, a decrease in learning capacity, or clumsiness.
However,

TRMPL1 : The Role Of TRPML1
Role of TRPML1 As mentioned before, TRPML1 is the transient receptor protein affected by the
mutation that causes MLIV. The TRP gene family are not yet well characterized, but are known to
localize in late endosomes and have associations with lysosomes. It is required for proper and
efficient fusion of late endosomes and autophagosomes with lysosomes (6). There were debates
regarding what sort of channel TRMPL1 was, with some stating that it was a proton channel rather
than an ion channel (2). However, it seems widely accepted that it is an ion channel capable
permeable to ions such as Ca2+ and Fe2+. There has also been recent research that further support
TRPML1 as an ion channel. Regardless, the precise role of TRPML1 is largely ... Show more
Genetics As mentioned before, MLIV is a rare autosomal recessive disorder. The gene affected is the
MCOLN1 gene, which is located on chromosome 19p13.2–13.3. The MCOLN1 gene is around 12
kb and contains 14 exons (1). The most common pathogenic variant of the mutation involves splice
variant c.406–2A>G. This splice variant prevents splicing of the mRNA encoding TRPML1 at exon
4, which results in abnormal mRNA (1). The second most common involves a deletion of 6.4 kb of
DNA, including exon 1 through 5 and a portion of 6 in the gene (1). Other variants include
frameshift and missense mutations in DNA sequences involving the MCOLN1 gene.
Molecular Diagnostics One test utilized in single–gene testing (1). Single–gene testing usually
utilize Sanger sequencing, followed by real time–PCR in order to detect deletions or duplications in
the DNA. Sanger Sequencing is the process DNA replication done in vitro with the use of chain–
terminating dideoxynuleotides alongside DNA polymerase. Real time–PCR is the process of
amplifying a single copy of DNA to point of gaining millions of copies of the DNA. Another test
utilized is a multi–gene panel, which screens not only for MCOLN1, but other genes of interest (1).
If use of single–gene testing and multi–gene panel fails to diagnose for someone with the
characteristics of MLIV, a more comprehensive genetic testing should be utilized. This includes
exome,

Morquio Syndrome In Freak The Mighty
Kevin, in Freak the Mighty, also known as Freak, has morquio syndrome. It stops him from doing a
lot of things "normal" people can do, but that's what makes his character so interesting. Morquio
syndrome is a genetic disorder. (Reuters, 19) It is one of a group of lysosomal storage disorders
scientifically known as mucopolysaccharidoses, or MPS IV–AI.(Reuters, 15) It is typically chronic
and progressive, and involves multiple organs of the body.(Reuters, 19) The chances of being born
with morquio syndrome are very low. There's about a 1 in 4 chance that your child will be born with
it, and that's only if both parents carry a nonworking copy of a gene related to this condition.
(Reuters, 19) But usually only one of the parents have this condition, and it's caused by a deficiency
of an enzyme known as N–acetylgalactosamine–6–sulfatase, which is based on genetics.(Reuters,
15) So it's a very, very, rare syndrome, estimated to occur in 1 ... Show more content on
Helpwriting.net ...
Many scientist have tried, but it's hard to replace what's never been there. There have been many
treatments that have been tried. A recent drug called Vimizim, which is made by BioMarin
Pharmaceutical Inc., is very helpful for patients with morquio type A.(Reuters, 19) It had an
improvement in energy and endurance, allowing the patients to better socialize, learn and function
independently.(Reuters, 19) After 24 weeks of treatment with the drug, Vimizim increased patients'
six–minute walk distance by 22.5 meters.(Reuters, 15) Vimizim has been given "orphan drug" status
by the FDA, which means it will receive seven years of market exclusivity if approved.(Reuters, 19)
An orphan drug treats diseases that affect fewer than 200,000 patients.(Reuters, 19) The main safety
concerns of the drug relate to anaphylaxis and allergic reactions.(Reuters, 19) The panel said such
side effects are consistent with other enzyme replacement therapies and that the benefits outweigh
the risks.(Reuters,

Metabolic Disorder Research Paper
Types of inherited Metabolic disorders
Lysosomal storage disorder
Spaces within cells which break down unwanted products of metabolism are called lysosomes.
Several enzyme deficiencies within lysosomes may lead to creation of toxic elements resulting in
metabolic disorders comprising–
Hurler syndrome – It is also known as abnormal structure of bone and delay in growth.
Niemann–Pick disease– It is a disease wherein which babies suffer from feeding difficulty, nerve
damage and develop enlargement of liver.
Tay–Sachs disease– it is a developing weakness within a months old baby, developing to severe
damage of nerve. In such cases a child usually does not live beyond the age of 5 years.
Gaucher disease– This disease involves, enlarged ... Show more content on Helpwriting.net ...
They are comprise of pain in extremities during childhood, with heart and kidney disease and stroke
in adulthood.
Krabbe disease– It refers to progressive damage of nerve, delayed development in young children
and occasional adverse effect on adults.
Galactosemia
Impaired break down of sugar galactose results in vomiting, jaundice and enlargement of liver post
breast feeding or forluma feeding to a newborn.
Maple syrup urine disease
In this disease, deficiency of BCKD enzyme results in creation of amino acids in our body. The
result is damaged nerves and smell of urine is like that of syrup.
Phenylketonuria or PKU
Deficiency of enzyme known as PAH leads to high amount of phenylalanine in our blood. The
results in mental retardation if not recognized early.
Glycogen storage diseases
Problem with storage of sugar causes low levels of blood sugar , pain in muscles and weakness.
Mitochondrial disorders
These are the problems within mitochondria which is the powerhouse of cells. This condition results
in damage of muscles.
Friedreich ataxia
Problems relevant to frataxin protein cause damage of nerves and often results in heart problems. It
can also lead to inability to walk from young

Hurrler Syndrome Case Studies

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