7 PKU

• Disorders of amino acid metabolism

  • Phenylketonuria
  • Maple syrup urine disease
• Phenylketonuria (PKU)


  An autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for phenylalanine hydroxylase
• When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate
• Phenylketonuria is the most common metabolic disorder in amino acid metabolism
• The incidence of PKU is 1 in 10,000 births
• Phenylketonuria primarily causes the accumulation of phenylalanine in tissues and blood
• Phenylacetate gives the urine a mousey odour
• The name phenylketonuria is due to the metabolite phenylpyruvate being a keto acid excreted in urine in high amounts
• Clinical manifestations of PKU

  Mental retardation<|>Failure to walk or talk<|>Failure of growth<|>Seizures<|>Tremor
• Effect on pigmentation in PKU

  Hypopigmentation causing light skin colour, fair hair, blue eyes
• Treatment of PKU


  1. Maintain plasma phenylalanine concentration

  2. Select low phenylalanine foods

  3. Feed synthetic amino acid preparations

  4. Adjust dietary intake by measuring plasma levels
• Early diagnosis and treatment for 4-5 years can prevent brain damage in PKU
• Tyrosine becomes essential in PKU patients as it cannot be synthesized
• Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids
• MSUD is caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC)
• Infants with MSUD seem healthy at birth but if left untreated suffer severe brain damage and eventually die
• Alkaptonuria is characterized by the accumulation of homogentisate in tissues and blood
• Alkaptonuria is not a dangerous disorder and does not require any specific treatment
• Tyrosinosis is due to the deficiency of fumarylacetoacetate hydroxylase and/or maleylacetoacetate isomerase
• Tyrosinosis causes liver failure, rickets, renal tubular dysfunction, and polyneuropathy
• In acute tyrosinosis, the infant exhibits diarrhea, vomiting, and 'cabbage-like' odor
• For the treatment of tyrosinosis, diets low in tyrosine, phenylalanine, and methionine are recommended