PKU

Question 1

Phenylketonuria is

Answer 1

example of single gene disorder,
• Inherited in an autosomal recessive (AR) manner
• It is considered one of the classic disorders
collectively called inborn errors of metabolism (IEM).
• The best known example of amino acid metabolic
disorders (part of IEM) is phenylketonuria.
• Children with phenylketonuria (PKU), if untreated,
have severe intellectual impairment and often
develop seizures.

Question 2

What is IEM?

Answer 2

Large group of diseases called (IEM)
• They exceed 200 diseases.
• Most follow autosomal recessive or X-linked
recessive inheritance, with only a few being
autosomal dominant.

Question 3

Group of IEM

Answer 3

• Amino-Acid Metabolism Æ e.g. PKU
• Urea Cycle Disorders
• CHO metabolism Æ e.g. galactosemia
• Glycogen Storage Diseases Æ e.g. Pompe disease
• Steroid metabolism Æ e.g. Congenital adrenal hyperplasia
• Lipid metabolism Æ e.g. Familial hypercholesterolemia
• Lysosomal Storage Diseases Æ e.g. Mucopolysaccharidosis
• Purine/Pyrimidine MetabolismÆ e.g. Lesch-Nyhan disease
• Porphyrin Metabolism Æ e.g. Acute intermittent porphyria
• Organic acid disorders
• Copper Metabolism Æ e.g. Wilson disease
• Peroxisomal disorders
• Disorders Involving Mitochondria
• Fatty acid oxidation disorders

Question 4

What are the main problems in patients with PKU?

Answer 4

1. Mental deficiency / intellectual impairment
2. Seizure disorder
3. Subsequent neurological abnormalities

Question 5

Clinical features of pku

Answer 5

What are the clinical features of PKU?
Classic PKU
1. Fair skin and fair hair with light-colored eyes.
2. Or Patchy hypopigmentation of hair.
3. Mental retardation and small head (microcephaly)
4. Seizures / convulsions (hyperactivity on EEG).
5. Severe learning disability
6. Mousy odor of urine and sweat
7. Eczema in some cases
8. Psychological disturbances

Question 6

Confirmatory tests available of pku

Answer 6

Plasma Amino Acid Analysis Æ Phe
• Organic Acid Analysis in urine Æ Phenylpyruvic
acid
• Enzyme assay Æ PAH
• Sequencing of Phenylalanine Hydroxylase (PAH)
Gene for PKU Æ detect mutation of the gene and
determine its type

Question 7

Screening test of pku called

Answer 7

Guthrie test

Question 8

Guthrie test

Answer 8

Screen for multiple common
inherited IEM, using a pin-
prick from newborn heel.

Few drops of blood are put on a
filter paper and then sent to the
laboratory for rapid testing.

Typically performed 2–7 days
after birth.

Question 9

Prevent pku

Answer 9

1.Termination of affected pregnancies (not valid).
2.Diagnosing and treating affected babies soon
after birth and preventing mental / learning
disability.
3.Advising affected families against
consanguineous marriages.