Phenylketonuria

Phenylketonuria

• Phenylketonuria is the most common metabolic disorder in amino acid metabolism.
• Due to the deficiency of enzyme phenylalanine hydroxylase.
• Inheritance- Autosomal recessive disorder
• It is of 5 types-

1. Type I (Classical phenylketonuria)- deficiency of phenyl hydroxylase
2. Type II & III (Atypical phenylketonuria)- deficiency of dihydrobiopterin reductase.
3. Type IV & V- deficiency of the enzyme synthesizing dihydrobiopterin.

Biochemical defect-

• Phenylalanine could not be converted into tyrosine.
• Phenylalanine level is increased in the blood.
• Alternative pathways are opened.
• Increased excretion of phenylalanine in urine gives the urine a mousy odour.

Clinical Defect-

• The classical PKU child is mentally retarded with low IQ.
• Failure of growth, seizures and tremors are the characteristics features.
• Defect in myelin formation is seen in PKU children.
• Accumulation of phenylalanine inhibits tyrosinase and impairs melanin formation resulting in hypopigmentation.
• Phenyl lactic acid in sweat may result in mousy body odour.

Diagnosis-

• Tandem mass spectroscopy
• Guthrie test- rapid screening test in blood.
• Ferric chloride test- identifies phenylketones in urine sample.
• DNA probe

Treatment-

• A low phenylalanine diet.
• Administration of 5- hydroxytryptophan and Dopa.
• Sapropterin dihydrochloride 

Nonclassical Phenylketouria-

• Due to Dihydrobiopterin Reductase Defect (Type II & Type III)
• Due to defect in the enzymes that synthesis of Tetrahydrobiopterin (Type IV & Type V)