A newborn's urine has a musty/mousy odour. Guthrie bacterial inhibition assay detects elevated phenylalanine. The child has a normal appearance but without treatment will develop intellectual disability. Which enzyme is deficient?
- A Homogentisic acid oxidase
- B Fumarylacetoacetate hydrolase
- C Phenylalanine hydroxylase ✓
- D Cystathionine beta-synthase
Explanation
Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase (PAH), the enzyme converting phenylalanine to tyrosine. Phenylalanine accumulates, producing alternative metabolites (phenylpyruvate, phenylacetate, phenyllactate) responsible for the musty/mousy odour and progressive neurological damage through multiple mechanisms including impaired myelination. Newborn screening by Guthrie bacterial inhibition assay detects elevated blood phenylalanine. Treatment is lifelong phenylalanine-restricted diet with supplementation of tyrosine and other amino acids. Homogentisic acid oxidase deficiency causes alkaptonuria (dark urine). Fumarylacetoacetate hydrolase deficiency causes tyrosinaemia type 1. Cystathionine beta-synthase deficiency causes homocystinuria (lens dislocation, Marfanoid habitus, thrombosis).
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.