Phenylketonuria Alkaptonuria Albinism

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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