This document summarizes a lecture on inborn errors of metabolism. It discusses various metabolic disorders affecting carbohydrate metabolism, including galactosemia caused by a defect in galactose-1-phosphate uridyltransferase, resulting in hypoglycemia, jaundice and mental retardation. It also discusses disorders of amino acid metabolism, such as phenylketonuria caused by phenylalanine hydroxylase deficiency, and homocystinuria caused by cystathionine synthase deficiency. Finally, it summarizes various fatty acid oxidation disorders caused by defects in fatty acid beta-oxidation pathways.
inborn errors of metabolism. Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food
This is a lecture note for 5th semester MBBS students. Lecture notes on hepatology, liver disease, alcoholic liver disease, alcohol-related liver disease, portal hypertension, and hepatic encephalopathy. Introduction to hepatic encephalopathy, causes, differentials, approach, and management of hepatic encephalopathy .
Inborn errors of metabolism
Definition:- Inborn errors of metabolism occur from a group of rare genetic disorders in which the body cannot metabolize food components normally.
These disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components.
inborn errors of metabolism. Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food
This is a lecture note for 5th semester MBBS students. Lecture notes on hepatology, liver disease, alcoholic liver disease, alcohol-related liver disease, portal hypertension, and hepatic encephalopathy. Introduction to hepatic encephalopathy, causes, differentials, approach, and management of hepatic encephalopathy .
Inborn errors of metabolism
Definition:- Inborn errors of metabolism occur from a group of rare genetic disorders in which the body cannot metabolize food components normally.
These disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
1. BCM 225 LECTURE ON
INBORN ERRORS OF METABOLISM
BY
OJEMEKELE O.
2. OUTLINE (week 11 and 12)
• Inborn errors of carbohydrate metabolism
• Inborn errors of amino acid metabolism
• Inborn errors of fatty acid metabolism
• Organic acidemias
• Lysosomal storage diseases
• Mitochondrial disorders
• Urea cycle disorders
• Blood chemistry; blood as a tissue
3. INBORN ERRORS OF METABOLISM
• Virtually every step of metabolic pathway is catalyzed
by an enzyme. Defect in enzymes of metabolic
pathways that result from abnormalities in their genes
are known as inborn errors of metabolism.
• The cause of enzyme defect are genetic mutations that
affect the structure and regulation of the enzyme, or
create problems with binding of cofactors.
• The consequences of an enzyme defect are
perturbations of cellular chemistry because of a
reduction in the amount of an essential product, the
build up of a toxic intermediate or the production of a
toxic side product.
4. INBORN ERRORS OF CARBOHYDRATE
METABOLISM
• These are inborn errors that affect the
catabolism and anabolism of carbohydrates.
• Carbohydrates account for a major portion of
the human diet and are metabolized into three
principal monosaccharides: galactose, fructose
and glucose.
5. GALACTOSEMIA
• Galactose is an aldohexose and is a constituent of lactose of milk.
Inability to metabolize galactose results in galactosemia.
• Classic galactosemia is caused by defect in the enzyme galactose-1-
phosphate uridyl transferase ; GAL-1-PUT (which catalyzes the rate
limiting step of galatose metabolism pathway).
BIOCHEMICAL IMPLICATIONS AND CLINICAL FEATURES
• Galactose-1-phosphate will accumulate in liver due to the block in
the enzyme (GAL-1-PUT). This will inhibit galactokinase as well as
glycogen phosphorylase, resulting in hypoglycemia.
• Bilirubin conjugation is reduced; so unconjugated bilirubin level is
increased in blood.
• There is enlargement of liver, jaundice and severe mental
retardation.
6. • Free galactose accumulates, leading to
galactosemia. It is partly excreted in urine
(galactosuria).
• Galactose is reduced to galactitol. The
accumulation of galactitol in the lens results in
cataract due to its osmotic effect.
• This is called congenital cataract and is a very
important feature of galactosemia
Summary : (hypoglycemia, jaundice and severe
mental retardation and cataract)
7. • A variant of galactosemia occurs due to the
deficiency of galactokinase. But here the
symptoms are milder.
• This is because galactose-1-phosphate is not
formed and hence toxic effects of this
compound (such as liver insufficiency,
hypoglycemia) are not manifested.
• Cataract is the only manifestations of galactose
kinase deficiency.
9. DIAGNOSIS AND MANAGEMENT
• Collection of fetal cells by amniocentesis may
be useful in prenatal diagnosis.
• Screening is also performed by measuring GAL-
1-PUT activity
• Management is by elimination of galactose
from the diet.
(Elimination of implicating substance; measuring
enzyme activity, amnioncentesis)
10. HEREDITARY FRUCTOSE INTOLERANCE
(HFI)
• HFI is caused by a defect in Aldolase B, hence fructose-1-
phosphate cannot be metabolized and will accumulate.
BIOCHEMICAL IMPLICATIONS AND SYMPTOMS
• Patients are asymptomatic unless they ingest fructose or
sucrose.
• Accumulation of fructose-1-phosphate will inhibit
glycogen phosphorylase. This leads to hypoglycemia.
• Vomiting and loss of appetite are seen.
• The infants often fail to thrive.
• Hepatomegaly and jaundice occur. If liver damage
progresses, death will occur.
DIAGNOSIS: Genetic testing and Aldolase B assay.
12. INBORN ERRORS ASSOCIATED WITH
GLUCOSE METABOLISM
• 1. Diabetes mellitus type 1 is a disorder caused by
reduced or absent levels of insulin, a hormone
that regulates the levels of glucose in blood.
• It causes hyperglycemia. Due to high osmotic
effect of high glucose levels, polyuria (excessive
urine output) results, this cause polydipsia
(excessive thirst).
• Diagnosis is by measuring blood glucose
concentrations
• Management can be achieved by insulin
replacement therapy
13. 2. Glucose 6-Phosphate dehydrogenase deficiency : is an
X-linked recessive hereditary disease characterised by
abnormally low levels of glucose-6-phosphate
dehydrogenase (abbreviated G6PD).
• G6PD is a metabolic enzyme involved in the pentose
phosphate pathway, especially important in red blood
cell metabolism.
• Individuals with the disease may exhibit non immune
hemolytic anemia in response to a number of causes,
most commonly infection or exposure to certain
medications or chemicals.
• Hemolytic anaemia can lead to paleness, hemolytic
jaundice, fatigue, shortness of breath and a rapid heart
rate.
14. GLYCOGEN STORAGE DISEASES (GSD)
• Enzyme deficiencies that leads to impaired synthesis or
degradation of glycogen are also considered disorders of
carbohydrates metabolism.
• The two organs most commonly affected are the liver and
the skeletal muscle
• Glycogen storage diseases that affect the liver typically
cause hepatomegaly and hypoglycemia, relating to
impaired mobilization of glucose for release to the blood
during fasting
• Those that affect skeletal muscle cause exercise intolerance,
progressive weakness and cramping resulting from low
glucose levels, hence there is inability to increase glucose
entry into glycolysis during exercise
16. DIAGNOSIS AND MANAGEMENT
• Diagnosis is achieved by evaluating blood glucose
levels, measurement of enzyme activity and
genetic testing
• Management; corn starch and sucrose
supplementation to increase blood glucose levels
have been suggested
• Gene therapy and enzyme replacement therapy
are currently been investigated as possible
therapies for GSDs
17. INBORN ERRORS OF AMINO ACID
METABOLISM
PHENYLKEKONURIA (PKU)
• This disease is caused by deficiency of phenyl alanine
hydroxylase (PAH). The enzyme that converts phenyl
alanine to tyrosine. Genetic mutation may be such that
either the enzyme is not synthesized, or a non-functional
enzyme is synthesized.
BIOCHEMICAL ABNORMALITIES
• Phenylalanine can not be converted to tyrosine. So
phenylalanine accumulates. Phenylalanine level in blood is
elevated.
• So, alternate minor pathways are opened (Fig 4) Phenyl
ketone (phenyl pyruvate), phenyl lactate and phenyl
acetate are produced from pheneylalanine which are are
excreted in urine.
18. Clinical Manifestations
• The classical PKU child is mentally retarded. The
mental retardation is caused by the accumulation
of phenylalanine (and its toxic metabolities
phenylpyruvate, phenyllactate and phenylacetate.
• Agitation, hyperactivity, tremors and convulsions
are often manifested. This may be because high
phenylalanine and low tyrosine levels reduces
neurotransmitter synthesis.
• The child often has hypopigmentation (low
melanin levels), explained by the decreased level of
tyrosine.
19. DIAGNOSIS
• Blood phenylalanine: Normal level is 1 mg/dl. In PKU, the level is
>20 mg/dl.
• Ferric chloride test: Urine of the patient contains phenyl ketone
This could be detected by adding a drop of ferric chloride to the
urine. Phenylketone reacts with ferric chloride to produce a
transient blue-green color.
MANAGEMENT
• PKU can be managed by providing a diet containing low in phenyl
alanine . Food based on tapioca (cassava) have low phenyl alanine
content.
• This special diet is to be continued during the first decade of life;
after which the child can have a normal diet. Life-long compliance of
special diet is recommended.
20. Fig 3: Tyrosine (a nonessential amino acid) is used not only for protein synthesis, but as
shown in the figure above, tyrosine is also the precursor for neurotransmitters;
dopamine,epinephrine , norepinephrine, thyroid hormones (T3&T4), as well as, skin
pigments (melanin).
22. ALKAPTONURIA
• This is due to the deficiency of the enzyme homogentisic acid oxidase(an enzyme
of tyrosine metabolic pathway) resulting in Homogentisic acid (HGA) accumulation
and excretion in urine.
• Alkaptonuria is an autosomal recessive condition with an incidence of 1 in 250,000
births.
• It is compatible with fairly normal life. The only abnormality is the blackening of
urine on standing. The homogentisic acid is oxidized by polyphenol oxidase to
benzoquinone acetate (Fig. 6). It is then polymerized to black coloured alkaptone
bodies.
• By the 3rd or 4th decade of life, patient may develop ochronosis (deposition of
alkaptone bodies in intervertebral discs, cartilages of nose, pinna of ear). Black
pigments are deposited over the connective tissues including joint cavities to
produce arthritis.
• DIAGNOSIS: 1.Urine becomes black on standing . Blackening is accelerated on
exposure to sunlight and oxygen. The urine when kept in a test tube will start to
blacken from the top layer.
2. Ferric chloride test will be positive for urine
• MANAGEMENT: Minimal protein intake with phenylalanine less than 500 mg/day
is recommended.
24. FIG 6: ALTERNATIVE OXIDATION OF
HOMOGENTISIC ACID IN ALKAPTONURIA
Black coloured
alkaptone bodies
Urine becomes
black on exposure
to air
25. ALBINISM
• Albinism is an autosomal recessive mutation in
the gene for tyrosinase (the rate limiting
enzyme of the melanin synthetic pathway),
resulting in absent of melanin (the pigment
that gives dark colour to the skin, hair and
eyes).
• A deficiency in tyrosinase will result in loss of
hair and skin pigments which explains the
albino phenotype.
26. • There is photophobia, nystagmus and decreased
visual acuity.
• The skin has low pigmentation, and so skin is
sensitive to UV rays. Hair is also white.
• Management includes use of tinted glasses to
reduce photophobia, use of sun protection
cream on the skin.
27. FIG 7: Melanin biosynthesis (reactions 1 and 2 are
catalyzed by tyrosinase)
28. HOMOCYSTINURIA
• Defect in cystathionine synthase (an enzyme
involved in conversion of methionine into
cysteine) leads to homocystinuria.
• It causes high concentration of homocysteine
and methionine in the blood. There is increased
excretion of methionine and homocystine in urine
and blood cysteine is markedly reduced.
• Homocysteine is highly reactive molecule hence
the disease is often associated with mental
retardation, multi systemic disorder of connective
tissue, muscle, CNS, and cardiovascular system.
29. • General symptoms are mental retardation, Skeletal
deformities. In eyes, ectopia lentis (subluxation of
lens), myopia and glaucoma may be observed.
Homocysteine causes activation of Hageman's factor.
This may lead to increased platelet adhesiveness and
life-threatening intra-vascular thrombosis.
• Diagnosis : Cyanide-nitroprusside test will be positive
in urine. Urinary excretion of homocystine is more
than 300 mg/24 h.
• Management : is a diet low in methionine and rich in
cysteine. Sometimes the affinity of apo-enzyme to the
co-enzyme is reduced. In such cases, pyridoxal
phosphate, the co-enzyme given in large quantities
(500 mg) will be useful.
32. MAPLE SYRUP URINE DISEASE
• It is also called branched chain ketonuria. The name originates from
the characteristic smell of urine (similar to burnt sugar or maple
sugar) due to excretion of branched chain keto acids.
BIOCHEMICAL DEFECT: Deficiency of branched chain alpha ketoacid
(BKA ) dehydrogenase complex
SYMPTOMS AND LABORATORY FINDINGS: Symptoms start in the first
week of life. It is characterized by convulsions, severe mental
retardation, vomiting, acidosis, coma and death within the first year
of life if not properly managed.
Urine contains branched chain keto acids derived from valine,
leucine and isoleucine.
DIAGNOSIS: Diagnosis is based on enzyme analysis in cells.
MANAGEMENT: Giving a diet low in branched chain amino acids
(valine, leucine and isoleucine).
33. FATTY ACID OXIDATION DISORDERS
(FAOD)
• Fatty acid oxidation disorders are genetic
conditions caused by mutations in genes that code
for enzymes responsible for oxidation of fatty
acids.
• When there is an alteration in these genes, enzyme
levels go down and fatty acids build up in the
blood.
• In the case of fatty acid oxidation disorders, the
inability to break down fats for energy and the
build up of fatty acids cause serious health
problems.
34. DIAGNOSIS: Babies can be tested (newborn screening) for fatty acid
oxidation disorders before they leave the hospital. The baby’s heel is
pricked and a few drops of blood are taken. The blood is sent to the state
laboratory to find out if it has more than a normal amount of fatty acids.
• There are various types of fatty acid oxidation disorders. The following is
a list of fatty acid oxidation disorders that can be screened for:
• Carnitine/Acylcarnitine Translocase deficiency (TRANS)
• Carnithine transporter deficiency (CTD)
• Long/Very Long Chain Acyl CoA Dehydrogenase deficiency (LCAD/VLACD)
• Medium Chain Acyl CoA Dehydrogenase deficiency (MCAD)
• Short Chain Acyl CoA Dehydrogenase deficiency (SCAD)
• Short-chain 3-Hydroxyacyl-CoA Dehydrogenase (SCHAD)
• Deficiency.
• Long-chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD)
35. Carnitine Transporter Deficiency (CTD).
• Although most of the fatty acid oxidation disorders affect
the heart, skeletal muscle and liver, cardiac failure is seen as
the major presentation in CTD .
• Over half of the known cases of CTD first present with
progressive heart failure and generalized muscle weakness.
• During the first years of life, extended fasting stress may
provoke an attack of hypoketotic hypoglycemic and coma.
This may lead to sudden unexpected infant death.
• Management: The outcome is usually very good with
carnitine therapy. Without carnitine therapy, the cardiac
failure can progress rapidly to death.
36. Medium-chain Acyl-CoA Dehydrogenase (MCAD)
Deficiency.
• This is the most common fatty acid oxidation disorder.
It is also one of the least severe, with no evidence of
chronic muscle or cardiac involvement.
• Affected individuals appear to be entirely normal until
an episode of illness is provoked by an excessive period
of fasting.
• Hypoglycemia develops because of excessive glucose
utilization due to the inability to switch to fat as a source
of energy. Severe symptoms of lethargy and nausea
develop in association with the marked increase in
plasma fatty acids.
38. • Very-long-chain Acyl-CoA Dehydrogenase
(VLCAD) Deficiency.
Many of the patients with VLCAD deficiency
have severe clinical manifestations, including :
• chronic cardiomyopathy
• weakness
• fasting coma.
39. ORGANIC ACIDURIAS
• They are disorders associated with metabolism of fatty
acids, branched chain amino acids , aromatic amino acids
and citric acid cycle.
• They are all characterised by the accumulation of organic
acids in body tissues and their excretion in urine.
• The patients present with acidosis, vomiting, convulsions
and coma. The children often die in infancy; in case they
survive, there is severe mental and growth retardation.
• Diagnosis is confirmed by showing the presence of organic
acids in urine by chromatography.
• Management : Dietary restriction, co- enzyme therapy and
substrate removal are the general lines of management.
40. SOME IMPORTANT ORGANIC
ACIDURIAS
Marple syrup Branched chain ketoacid convulsions, mental
Urine disease dehydrogenase retardation, acidosis,
vomiting , coma
42. MITOCHONDRIAL DISEASES
• Mitochondrial diseases are group of disorders caused by
mutations in mitochondrial DNA (mtDNA) or in nuclear
genes that code for mitochondrial proteins.
SYMPTOMS
• Poor growth, muscle weakness, heart problems, liver
disease, kidney disease, respiratory disorders,
neurological problems.
• Mitochondria diseases are worse when the defective
mitochondria are present in the cells of muscles,
cerebrum or nerves, because these cells use more energy
than most other cells in the body. Recall that
mitochondria are double membrane cellular organelles,
responsible for producing cellular energy (ATP) by
oxidative phosphorylation.
43. EXAMPLES OF MITOCHONDRIAL
DISEASES
• Mitochondrial myopathy (disease of muscles)
• Leber’s hereditary optic neuropathy (LHON)
usually characterized by deterioration in vision
• Leigh syndrome: clinical features include
encephalopathy (disorder that affects the brain),
seizures, dementia.
• Mitochondrial encephalomyopathy with lactic
acidosis and stroke-like episodes (MELAS)
44. DIAGNOSIS
• Genetic testing: Although high levels of
mutations can be detected in blood, it is
always advisable to use muscle for detecting
mtDNA mutations, because it contains much
mitochondria.
MANAGEMENT
Coenzyme Q and creatine supplementation.
Coenzyme Q plays important role in oxidative
phosphorylation. Creatine enhances ATP
production in muscle cells.
45. UREA CYCLE DISORDERS
• The urea cycle disorders (UCD) result from
mutations in genes that code for enzymes of urea
cycle.
• This leads to defects in the metabolism of the
extra nitrogen produced by the breakdown of
protein and other nitrogen-containing molecules.
• Severe deficiency or total absence of activity of
any of the first four enzymes (CPSI, OTC, ASS, ASL)
in the urea cycle or the cofactor producer (NAGS)
results in the accumulation of ammonia and
other precursor metabolites during the first few
days of life.
47. Symptoms of Newborns with Urea Cycle Defects
• Normal appearance at birth
• Irritability progressing to lethargy and later
coma
• Loss of thermoregulation (hypothermia)
• Neurologic posturing (from cerebral edema)
• Seizures
• Hyperventilation and then hypoventilation
49. DIAGNOSIS
• The most important step in diagnosing urea cycle
disorders is clinical suspicion of hyperammonemia.
A blood ammonia level is the first laboratory test
in evaluating a patient with UCD
• Enzymatic and genetic diagnosis
MANAGEMENT
• Fluids, dextrose to mitigate dehydration
• Remove protein from intake
• Dialysis is very effective for the removal of
ammonia from blood.
50. LYSOSOMAL STORAGE DISEASES (LSD)
• Lysosomes are involved in the degradation and recycling of
extracellular material (via endocytosis) and intracellular
material (via autophagy).
• Lysosomal storage diseases (LSDs) describe a group of rare
inherited metabolic disorders that result from the defect
in lysosomal hydrolases or transporters, resulting in the
progressive accumulation of undigested material in
lysosomes.
• The accumulation of these substances affects the function
of lysosomes and other organelles, resulting in secondary
alterations such as impairment of autophagy,
mitochondrial dysfunction, inflammation and apoptosis.
• LSDs frequently involve the central nervous system (CNS),
where neuronal dysfunction or loss results in progressive
neurodegeneration and premature death.
51. Gaucher’s disease
• Gaucher's disease is a sphingolipidosis resulting
from glucocerebrosidase deficiency, causing
deposition of glucocerebroside and related
compounds.
• Type I (non-neuronopathic) is the adult form of
the disease. Onset ranges from age 2 yr to late
adulthood.
• Type I Gaucher's disease cause anemia, fatigue,
lung impairment and kidney impairment.
52. • Type II (acute neuronopathic) is very rare and residual enzyme
activity in this type is lowest. Onset occurs during infancy. Type II
Gaucher's disease causes severe neurological disorder, liver
enlargement and spleen enlargement.
• Type III (subacute neuronopathic) falls between types I and II in
incidence, enzyme activity and clinical severity. Type III Gaucher's
disease cause progressive brain damage and seizures.
Diagnosis : is by enzyme analysis of WBCs.
Treatment:
• Enzyme replacement with placental or recombinant
glucocerebrosidase is effective in types I and III; there is no
treatment for type II disease.
• An oral treatment drug for Gaucher's disease (Zavesca/Miglustat)
was licensed by the European authorities in April 2003 for those
patients deemed unsuitable for enzyme replacement[
53. Tay-sachs disease
• Gangliosides are complex sphingolipids present in the brain.
There are 2 major forms, GM1 and GM2 . Taysachs disease is
caused by the deficiency of hexosaminidase A (an enzyme
that breaks down GM2) results in accumulation of GM2 in
the brain.
• Children develop progressive cognitive and motor
deterioration resulting in seizures, mental retardation and
paralysis.
• Diagnosis is clinical and can be confirmed by enzyme assay.
• Treatment : Hexosaminidase A from human urine infused
intravenously in patients with Tay-Sachs disease results in
43% reduction in the elevated quantity of globoside in the
circulation.
54. Niemann-pick disease
• Niemann-Pick disease is a rare inherited autosomal recessive
disease cause by defect in acid sphingomyelinase, this results in
accumulation of sphingomyelin in lysosomes.
• Type A Niemann-Pick disease is a severe neurodegenerative
disorder of infancy that leads to death by age 3 years. Patients have
enlarged liver and spleen.
• Type B disease has a later age at onset, little or no neurologic
involvement, and survival of most patients into adulthood. Patients
also have enlarged liver and spleen.
.
• Diagnosis: Prenatal diagnosis of Niemann-Pick disease types A and
B is routinely accomplished by sphingomyelinase assay.
• Treatment: At present no specific treatment is available for patients
with any Niemann-Pick disease subtypes and treatment is
symptomatic. Bone marrow transplantation in a patient with
Niemann-Pick disease type B was successful in reducing spleen and
liver volumes
55. Sandhoff’s disease
• Sandhoff’s disease is caused by the combined deficiency
of hexosaminidase A and B.
• Clinical manifestations include progressive cerebral
degeneration beginning at 6 months accompanied by
seizures, blindness, cherry-red macular spot and
hyperacusis (a hearing disorder in which patients cannot
tolerate normal environmental sound).
• Diagnosis involves a test to measure enzyme activity of
the two hexosaminidase . If the enzyme activity results
indicate that there is no hexosaminidase activity, it
means that the patient has Sandhoff disease. However, if
there is still B subunit activity, then this indicates that
the patient might have Tay-Sachs disease.
56. BLOOD AS A TISSUE
• Blood is a liquid connective tissue
• The total blood volume makes up about 6-8
percent of the body’s weight
• A 70kg person has approximately 5 to 6 litres of
blood.
• Normal pH of blood is 7.35(venous blood)-7.45
(arterial blood)
57. BLOOD COMPOSITION
• Blood consists of:
Liquid plasma (volume 55-60%)
Formed elements or cells (volume 40-45)
The formed elements include red blood cells,
white blood cells and platelets
58. ERYTHROCYTES
• Red blood cells or erythrocytes are the most
abundant type of blood cell
• They are involved in the transport of oxygen
and carbon dioxide.
• They lack nucleus and mitochondria in order
to accommodate maximum space for
hemoglobin
59. LEUKOCYTES
• Leukocytes or white blood cells have nuclei
• The major function of leukocytes is protective
function, they provide immunity and thus
defends the body
• Lymphocytes, neutrophils, monocytes,
eosinophils and basophils are types of
lymphocytes
60. PLATELETS
• These are tiny cell fragments
• They play critical roles in blood clotting
• They are produced in the bone marrow by
large cells called megakarocytes
61. SERUM AND PLASMA
• Serum is the liquid portion of blood obtained
after centrifugation of coagulated blood.
Serum therefore lacks clotting factors.
• Plasma on the other hand is the liquid portion
of blood obtained by centrifuging blood
sample that has been treated with
anticoagulant (such as EDTA, heparin). Plasma
therefore has clotting factors.
62.
63. FUNCTIONS OF BLOOD
• TRANSPORTATION of dissolved gases (Carbon
dioxide and oxygen), nutrients, hormones and
metabolic wastes.
• PROTECTION
Platelets in the blood minimize blood loss
when a blood vessel is damaged
White blood cells protect the body against
infectious diseases