Phenylketonuria Alkaptonuria Albinism

1. Molecular basis of disease
Presented by
S.Mohammed Razeeth

2. Molecular basis of
disease?

3. Discussion
Phenylketonuria
Alkaptonuria
Albinism

4. 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

5. Metabolic pathway

6. 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.

7. 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

8. 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.

9. Guthrie test

10.  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.

11. Treatment

12. pku

15. Alkaptonuria

16. 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.

18. 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.

19. 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.

21. 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.

25. 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

26. 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.

27. Albinism

28. 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

29. 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,

30. Types
Two types
Oculocutaneous albinism
Ocular albinism

31. In oculocutaneous albinism pigment is
lacking in the eyes, skin and hair.
In ocular albinism, only the eyes lack pigment

33. 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

36. Thank you
Meet again