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Molecular basis of disease
Presented byS.Mohammed Razeeth
Molecular basis of disease?
Discussion
Phenylketonuria
Alkaptonuria
Albinism
Phenylketonuria
PKU is an inherited disorder that increases the levels of phenylalanine in the blood
Due to defictive hepatic enzyme phenylalanine hydroxylase (PAH) .
Necessary to metabolize the amino acid phenylalanine ('Phe') to the amino acid tyrosine
Metabolic pathway
Symptom
Early diagnosis is essential because symptoms are not obvious in a newborn infant.
Mental retardation may develop gradually
An early clue to the disease is light coloring of the skin, eczema (an itchy skin rash), and a musty odor.
Other symptoms may include
Delayed mental and social skills Head size significantly below normal Hyperactivity Jerking movements of the arms or legs Mental retardation Seizures Skin rashes Unusual positioning of hands
Diagnosis of Phenylketonuria
PKU is normally detected using the HPLC test
Guthrie test Devised by Dr Robert Guthrie (1916 - 1995)
after the birth of his own child with PKU.
Guthrie test
A small drop of blood is taken from the heel of a newborn and applied to a card
A small portion of the dried disc is incubted on a petri dish plated with Bacillus subtilis bacteria in the presence of a growth inhibitor, B-2-thienyl-alanine.
The presence of high levels of Phe in the blood sample overcomes the inhibition, and allows the bacteria to grow.
Treatment
pku
Alkaptonuria
Alkaptonuria
Alkaptonuria -black urine disease is a rare inherited genetic disorder of phenylalanine and tyrosine metabolism.
Due to a defect in the enzyme homogentisate 1,2-dioxygenase.
What genes are related to alkaptonuria?
Mutations in the HGD gene cause alkaptonuria.
The HGD gene provides instructions for making an enzyme called homogentisate oxidase.
Mutations in the HGD gene impair the enzyme's role in this process.
How do people inherit alkaptonuria?
This condition is inherited in an autosomal recessive pattern
which means both copies of the gene in each cell have mutations.
The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Signs and symptoms
It is asymptomatic, but later sclera of the eyes may be pigmented the skin may be darkened in sun-exposed
areas Urine may turn brown if collected and left
exposed to open air. The accumulation of homogentisic acid in
tissues.
Diagnosis
Diagnostic testing can be performed using paper chromatography and thin layer chromatography
Both blood plasma and urine can be used for diagnosis.
In alkaptonuria plasma levels are 6.6 micrograms/ml on average, and urine levels are on average 3.12 mmol/mmol of creatinine
Treatment
No treatment demonstrated to reduce the complications.
Recommended treatments include dietary restriction of phenylalanine and tyrosine.
Large doses of ascorbic acid (vitamin C). Must taken.
Albinism
Albinism is a congenital disorder.
complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin
causes
Most forms of albinism are due to recessive alleles (genes) passed from both parents of an individual, though some rare forms are inherited from only one parent.
Mutation can also cause albinism.
Affect all vertebrates,
Types
Two types
Oculocutaneous albinism
Ocular albinism
In oculocutaneous albinism pigment is lacking in the eyes, skin and hair.
In ocular albinism, only the eyes lack pigment
Symptom
Light hair Light skin Light-colored eyes Reduced pigmentation in iris Reduced retinal pigmentation Vision problems Reduced visual acuity Involuntary eye movements Increased light sensitivity
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