The document discusses several inborn errors of aromatic amino acid metabolism including phenylketonuria (PKU), alkaptonuria, tyrosinemia types I, II, and III, and albinism.
PKU is caused by a deficiency of the enzyme phenylalanine hydroxylase leading to a buildup of phenylalanine. Left untreated it causes intellectual disability. Newborns are screened for PKU and treatment involves a low-phenylalanine diet.
Alkaptonuria is caused by a deficiency of homogentisate 1,2-dioxygenase leading to a buildup of homogentisic acid and later joint and skin pigmentation problems. There is
Alkaptonuria is a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body. Affected individuals lack enough functional levels of an enzyme required to breakdown homogentisic acid. Affected individuals may have dark urine or urine that turns black when exposed to air.
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.
Protein which are major component of our diet have amino acid as their precursor and also act as important energy source. Any imbalance in the metabolism of these amino acid cause disorders
Inborn errors of amino acid metabolismRamesh Gupta
Inherited disorders of amino acid metabolism e.g. phenylketonuria, maple syrup urine disease, alkaptonuria, homocystinuria, Hartnup disease etc for medical, biochemistry and biology undergraduates
Alkaptonuria is a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body. Affected individuals lack enough functional levels of an enzyme required to breakdown homogentisic acid. Affected individuals may have dark urine or urine that turns black when exposed to air.
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.
Protein which are major component of our diet have amino acid as their precursor and also act as important energy source. Any imbalance in the metabolism of these amino acid cause disorders
Inborn errors of amino acid metabolismRamesh Gupta
Inherited disorders of amino acid metabolism e.g. phenylketonuria, maple syrup urine disease, alkaptonuria, homocystinuria, Hartnup disease etc for medical, biochemistry and biology undergraduates
Aromatic amino acids (AAA)- are amino acids that include an aromatic ring.
Examples include:
Among 20 standard amino acids:
phenylalanine (phe)
tryptophan (trp)
histidine (His)
tyrosine (tyr)
All plants and micro-organisms must synthesize their aromatic amino acids through the shikimate pathway in order to make proteins, unlike animals, which obtain them through their diet.
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. A birth defect that causes an amino acid called phenylalanine to build up in the body.
Newborns should be screened for PKU.
Untreated phenylketonuria can lead to brain damage, intellectual disabilities, behavioural symptoms or seizures.
Treatment includes a strict diet with limited protein.
Definition:
Many childhood conditions are caused by gene mutations that encode specific proteins. These mutations can result in the alteration of primary protein structure or the amount of protein synthesized.
The functional ability of protein, whether it is an enzyme, receptors, transport vehicle, membrane, or structural element, may be relatively or seriously compromised.
These hereditary biochemical disorders are collectively termed as ‘’Inborn errors of metabolism’’
Aromatic amino acids (AAA)- are amino acids that include an aromatic ring.
Examples include:
Among 20 standard amino acids:
phenylalanine (phe)
tryptophan (trp)
histidine (His)
tyrosine (tyr)
All plants and micro-organisms must synthesize their aromatic amino acids through the shikimate pathway in order to make proteins, unlike animals, which obtain them through their diet.
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. A birth defect that causes an amino acid called phenylalanine to build up in the body.
Newborns should be screened for PKU.
Untreated phenylketonuria can lead to brain damage, intellectual disabilities, behavioural symptoms or seizures.
Treatment includes a strict diet with limited protein.
Definition:
Many childhood conditions are caused by gene mutations that encode specific proteins. These mutations can result in the alteration of primary protein structure or the amount of protein synthesized.
The functional ability of protein, whether it is an enzyme, receptors, transport vehicle, membrane, or structural element, may be relatively or seriously compromised.
These hereditary biochemical disorders are collectively termed as ‘’Inborn errors of metabolism’’
What is a metabolic disease?
Inborn errors of metabolism”
inborn error : an inherited (i.e. genetic) disorder
metabolism : chemical or physical changes in a biological system
Metabolism of amino acids (general metabolism)Ashok Katta
Metabolism of amino acids (general metabolism).
Part - I of amino acid metabolism.
This presentation covers Transamination, deamination, formation and Transport of Ammoniaand etc.
INBORN ERRORS OF METABOLISM, PKU, PHENYLKETONURIA, BY: MR. DINABANDHU BARAD, MSC TUTOR, SUM NURSING COLLEGE, SIKSHA O ANUSANDHAN DEEMED TO BE UNIVERSITY, BHUBANESWAR, ODISHA
Screening for any disorder in individuals is a strategy used for identifying a disease before the onset of signs or symptoms, thus enabling earlier detection and management with the aim to reduce morbidity and mortality.
designed for undergraduate level teaching of nitrogen metabolism focusing on amino acid metabolism in biochemistry. this is second in the series of three lectures. ideal for MBBS level teaching
nausea and vomiting in pregnancy is very common. it may be a manifestation of some medical - surgical - gynecological complications. hyperemesis gravidarum is a severe type of vomiting in pregnancy which has got deleterious effects on the health of the mother. it is a very important topic and it is also a topic in obstetrics. we should encourage and help young mothers to identify the symptoms. please read it and get knowledge about nausea and vomiting in pregnancy. stay tuned.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
- 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
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
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.
2. • A 1 yr old girl is brought to her pediatrician’s office with
concerns about her development. She had an uncomplicated
birth at term. The mother reports that the baby is not
achieving the normal milestones for a baby of her age. She
also reports an unusual odor to her urine and some areas of
hypopigmentation on her skin and hair. On examination, the
girl is noted to have some muscle hypotonia and
microcephaly. The urine collected is said to have mousy odor.
• What is the most likely diagnosis ?
• PHENYLKETONURIA
3. • Autosomal recessive
• Metabolic genetic disorder
• Incidence of 1 in 10,000 live births ( 1 in 18,300 in India )
• Mutation in the gene coding for phenylalanine hydroxylase
(PAH)
• It is this enzyme that is necessary to convert phenylalanine
into another amino acid called tyrosine
• If this chemical pathway can not occur, phenylalanine builds up
in the bloodstream and brain tissue, causing mental
retardation and central nervous system problems
• Discovered by Norwegian physician Ivar Folling , thus also
called as Folling’s disease
4.
5. Normal serum phenylalanine levels
are 1 to 2 mg%
Increase in phenylalanine levels
Decrease in tyrosine levels
6. Signs & Symptoms
• Untreated children are normal at birth , but fail to attain early
developmental milestones
• Seizures
• Microcephaly
• Progressive impairment of cerebral function
Executive function ( cognitive abilities )
Information processing speed
ADHD ( late manifestation )
Learning disabilities( late manifestation )
basically untreated PKU show symptoms of mental retardation
by the age of 1 yr
• Musty or Mousy odor of skin ,hair ,sweat and urine (due to
phenylacetate accumulation)
• Tendency towards hypopigmentation and eczema
12. Newborns are screened for PKU
• All US babies are screened for PKU by
heel-prick test.
• Performed 2-7 days after birth and repeat
at 2 weeks of age.
• Blood tested for excess phenylalanine.
• Blood placed on agar plate with bacteria
that need phenylalanine to grow.
• Healthy babies’ blood doesn’t have extra
phenylalanine, so bacteria can’t grow
• Babies with PKU have extra
phenylalanine, so bacteria grow
13. Guthrie test for PKU
Bacterial plate with newborn blood samples
Negative controls: no bacterial
growth
Positive blood test results: bacterial
halo = PKU
Negative blood test results: no
bacterial growth = healthy babies
Positive controls : increasing
phenylalanine concentrations give
bacterial halos
http://www.childrenshospital.org/cfapps/research/data_admin/Site2940/mainpageS2940P4sublevel15.html
14.
15. • Infants may still be breastfed to provide the benefits of breast
milk , but quantity should be monitered
• Top fed with special infant formula called Lofenalac ( low in
phenylalanine )
• Kuvan ( sapropterin dihydrochloride , BH4 ,
tetrahydrobiopterin)
• Glycomacropeptide ( protein derived from goat milk , which is
free of Phe , but it is to be substituted with Tyr and Trp )
• Large neutral amino acid therapy ( LNAA )
16. Sickenly sweet Aspartame
• Aspartame = artificial sweetener made from
amino acids phenylalanine and aspartic acid
• Found in “diet”, “light”, and “sugar-free” foods
• Highly toxic to people with PKU
17.
18. Other modalities of treatment
• Enzyme substitution therapy ( PEG-PAL ) : Phenylalanine
ammonia lyase is joined to polyethylene glycol.
PAL breaks down Phe to transcinnamic acid and ammonia
which further break down into non-toxic compounds that can
be easily handled by the body.
• Therapeutic liver cell ( hepatocyte ) repopulation
• Gene therapy
19.
20. Types of hyperphenylalaninemia
• Classical PKU
400 disease causing mutations have been seen on the PAH
gene located on chromosome number 12
• Persistent hyperphenylalaninemia
Decreased PAH enzyme activity , can be managed by
temporary dietary therapy
• Transient mild hyperphenylalaninemia
Maturational delay in PAH enzyme
• Tetrahydrobiopterin-deficient hyperphenylalaninemia
21. Tetrahydrobiopterin-deficient hyperphenylalaninemia
• Rare form of hyperphenylalaninemia when PAH is normal
• Defect in the gene coding for dihydrobiopterine reductase , thus
BH4 cannot be replinished and made available for PAH enzyme for
its activity.
• Additional supplements required
• Differentiate with the help of prolactin levels ( prolactin levels
normal in treated classical PKU )
23. Alkaptonuria
• Also known as Black bone disease or Black urine disease
• Autosomal recessive inheritance
• Metabolic genetic disorder
• Incidence is 2 to 5 per million live births
• Deficiency in homogentisate 1,2-dioxygenase, an enzyme
which converts homogentisic acid (HGA ) to maleylacetoacetic
acid in the tyrosine degradation pathway
• Accumalation of HGA at 2000 times the normal rate
• The gene coding for homogentisate 1,2-dioxygenase is located
on chromosome number 3
• First described by Sir Archibald Garrod in 1901 in London as
one of his tetrad
24.
25. • Alkaptonuria has three major features :
1) HGA accumulates in the blood and appears in the urine, which on
standing is oxidized to a black pigment (alkapton), hence the name
Black urine disease
2) Ochronosis ( bluish-black pigmentation of connective tissue )
Accumulation of HGA and its oxidation product benzoquinone
acetate in the connective tissue
• Brown pigmentation of the sclera is observed midway between
the cornea and the outer and inner canthi at the insertin of the
recti muscles. Pigment deposition may also be seen in the
conjunctiva and cornea. The pigmentation does not affect vision .
• Ear cartilage pigmentation is first seen in the concha and antihelix,
and later in the tragus. The cartilage is slate blue or gray and feels
irregular or thickened. Calcification of the ear cartilage may be
observed on radiographs.
• Pigment also appears in cerumen and in perspiration, causing
discoloration of clothing.
• A deep purple discoloration may be seen on the skin of the hands,
corresponding to the underlying tendons, or in the web between
the thumb and index finger.
3) Arthiritis
26. Natural History
• During childhood , AKU is asymptomatic apart from the urine
turning dark on standing
• AKU does not cause cognitive impairment or developmental
delay
• From the third decade of life signs and symptoms due to
ochronosis begin to manifest ( low back pain may be the
presenting symptom at this age indicating the involvement of
the spine )
• By the fifth decade arthritis manifests in the large joints
• Other organ involvement
Aortic and Mitral Valve calcification
Renal stones and Prostate stones
27. Diagnosis
• Biochemical testing. The diagnosis of alkaptonuria is based on
the detection of a significant amount of HGA in the urine by
gas chromatography-mass spectrometry analysis. The amount
of HGA excreted per day in individuals with alkaptonuria is
usually between one and eight grams .
• A normal 24-hour urine sample contains 20-30 mg of HGA.
• HGD molecular genetic testing to confirm the diagnosis
• Prenatal diagnosis in high-risk families
28. Treatment
• No cure for AKU
• Only treatment offered to patients is palliative, pain management
till joint collapse and joint replacement surgery
• Important to avoid sports and exercise that put too much stress on
joints
• Dietary restriction does not help much , but red meat can be
avoided just to control the Phe and Try levels
• Nitisinone a triketone herbicide an inhibitor of 4-hydroxyphenyl
dioxygenase , the enzyme that produces HGA
Drug approved for the use in tyrosinemia type 1 , clinical trials
going on for its use in AKU
Reduces HGA formation at the expense of elevated Tyr levels ,
which may cause photophobia and rarely corneal crystals
30. Tyrosinemia type I
• Also known as hepato-renal tyrosinemia / Tyrosinosis /
Hereditary infantile Tyrosinemia
• Most severe form of tyrosinemia
• It is inhereted in an autosomal recessive pattern with an
incidence of 1 in 1,00,000 ( incidence is quite common in
Quebec ,Canada of 1 in 16,000 )
• Deficiency of enzyme fumaryl acetoacetate hydrolase
• This leads to build up of fumaryl acetoacetate and succinyl
acetone
• This enzyme is expressed more in the liver and proximal renal
tubular epithelial cells
31.
32. Pathophysiology
• Fumaryl acetoacetate along with its metabolites accumulate
in the hepatocytes and renal tubular cells, causing oxidative
damage and DNA damage along with dysfunctional gene
expression which alters the metabolic processes like protein
synthesis and damages these organs
• The symptoms of Tyrosinemia type 1 are due to accumulation
of tyrosine and its metabolites ( Succinylacetone,
Succinylacetoacetate and fumarylacetone ) in the liver, kidney
and central nervous system
• Succinylacetone inhibits enzyme δ-ALA dehydratase in the
liver and circulating RBC’s
33. Signs and Symptoms
• The so-called acute form is present at birth or during the few first months
of life.
• Infants with the acute form of tyrosinemia type 1 exhibit rapid onset of
symptoms,
• usually beginning with failure to thrive. Additional early symptoms
include:
• • Fever
• • Diarrhea/bloody stools
• • Vomiting
• • Enlarged liver
• • Tendency to bruise easily
• • Jaundice
• • Lethargy
• • Irritability
• • Some infants may have a distinctive cabbage-like odor to the skin and
urine
Untreated acute tyrosinosis progress towards life-threatening liver
failure and succumb to the same by 8 months of age
34. • Chronic form of Tyrosinemia type 1
Characterized by a more gradual onset
and less severe expression of symptoms
Present with hepato-splenomegaly and
failure to thrive
Developmental delay and repeated
acute neurological
episodes like acute polyneuropathy and
altered mental status
Cirrhosis of liver ( increased risk of HCC )
Renal Fanconi syndrome
• Untreated chronic cases survive upto 10
years of age
35. Diagnosis
• Diagnosed as a result of newborn screening
• Suspicion of diagnosis in infants who display failure to thrive
and hepatomegaly in first 3 months of life
• Detection of Succinylacetone in urine and decreased activity
of FAH enzyme in liver tissue or cultured fibroblasts confirms
the diagnosis
• Elevated plasma Tyrosine, Phenylalanine and Methionine
levels
• Increased urinary excretion of δ-ALA
• Markedly elevated AFP
• Prolonged PT and pTT
• Prenatal diagnosis : Succinylacetone levels in amniotic fluid
and FAH enzyme activity in amniotic fluid cells.
36. Treatment
• Prompt indentification and treatment may prevent severe
liver, kidney and neurological problems and child can
experience a normal growth
• 1) Dietary treatment : Low protein diet that contains limited
amounts of Phe and Tyr
• 2) Medical Treatment : Nitisinone, inhibitor of 4-
hydroxyphenylpyruvate dioxygenase.
• 3) Liver transplant : infants with end stage liver failure
37. Tyrosinemia Type II
• Also known as Oculocutaneous Tyrosinemia / Richner Hanhart
Syndrome
• Autosomal recessive inheritance
• Deficiency of enzyme tyrosine aminotransferase due to
mutation in the gene located on chromosome number 16
• Incidence is 1 in 2,50,000
• It affects the eyes , skin and mental development
• Manifestations are due to accumulation of tyrosine and its
metabolites by an unknown mechanism
38.
39. Clinical Manifestation
• Excessive lacrimation, redness, pseudodendritic keratitis,
corneal deposits, corneal ulcers followed by scarring
Usually manifest in the first year of age
• Non-pruritic , hyperkeratotic papules and plaques principally
located on palms and soles ( palmoplantar hyperkeratosis ).
The lesions are painful and progressive and associated with
hyperhidrosis
Usually manifest after 1 year of age
• Central nervous system involvement is variable and usually
manifests as intellectual deficit
40.
41. Diagnosis and Treatment
• Detection of high levels of plasma and urinary tyrosine
• Management :
Dietary limitation of Phe and Tyr.
Oral retinoids for skin lesions.
Oculocutaneous manifestations resolve with dietary
control.
Its unknown wether CNS symptoms resolve with dietary
control.
42. Tyrosinemia type III
• Very rare disorder
• Autosomal recessive inheritance
• Deficiency of enzyme 4-hydroxyphenylpyruvate dioxygenase,
leading to accumulation of 4-hydroxyphenylpyruvate and its
metabolites like 4-hydroxyphenylacetate and 4-
hydroxyphenyllactate along with increased plasma levels of
tyrosine
• Deficiency is due to mutation in the gene coding for the
enzyme , locate don chromosome number 12
• It is characterized by mild mental retardation, seizures and
intermittent ataxia observed during the infancy period
• Not much is studied about the disease
45. Albinism
• It is a group of genetic disorder that is potrayed by the
absence or diminished pigmentation in the skin, eyes and hair
of the organism.
• Albinism at first was considered an innate error of metabolism
in the genetic makeup of organisms in 1908 by scientist Sir
Archibald Garrod
• Two general types :
1) Ocular Albinism
2) Oculocutaneous Albinism
46.
47.
48. Signs and Symptoms
• It affects the pigmentation of skin, hair and eyes
• Visual problems :
1) Photophobia & decreased visual acuity
2) Nystagmus , Astigmatism
3) Strabismus
4) Optic Chiasma abnormalities
The above manifestations are because poor development of
retinal pigment epithelium and foveal hypoplasia
Iris, being pigmented normally controls the amount of light
falling on the retina ( through pupil ).
In albinism the iris is completely trans-illuminated and and
displays the colour of retina itself
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65. • Gene Therapy
▫ Improve visual acuity by implementing healthy OA1 protein into the
RPE cells (Anderson, et. al, 2004).
▫ This enriched visual acuity and improving overall eye sight of those
affected with albinism (Anderson, et. al, 2004).