Disorders of amino acid metabolism

Disorders of amino acid metabolism are inborn errors of metabolism: genetic defects, most inherited in an autosomal recessive pattern, that disable an enzyme in an amino acid's degradation or conversion pathway. The blocked step causes the upstream substrate to accumulate to toxic levels while downstream products become deficient, and the clinical picture follows from which pathway is broken.

The prototype is phenylketonuria (PKU), a deficiency of phenylalanine hydroxylase that prevents conversion of phenylalanine to tyrosine. Untreated, phenylalanine buildup causes intellectual disability, seizures, a musty body odor, and fair pigmentation; treatment is lifelong dietary phenylalanine restriction with tyrosine supplementation. Other high-yield examples include maple syrup urine disease (branched-chain ketoacid dehydrogenase deficiency, with sweet-smelling urine and neurotoxicity from leucine), homocystinuria (classically cystathionine synthase deficiency, with marfanoid habitus, lens dislocation, and thrombosis), alkaptonuria (homogentisate oxidase deficiency, with dark urine and ochronosis), and cystinuria (defective renal transport causing cystine kidney stones).

These conditions matter clinically because many are detectable by newborn screening and treatable with dietary management before irreversible neurologic damage occurs — PKU is the textbook success story of population screening.

USMLE Step 1 tests these disorders heavily in biochemistry. Expect vignettes pairing a characteristic finding — musty odor, sweet urine, lens dislocation, urine that darkens on standing — with the deficient enzyme, the accumulating metabolite, and the inheritance pattern.