Menkes disease (kinky hair disease) is caused by mutations in ATP7A, a copper-exporting ATPase in intestinal enterocytes. Which copper-dependent enzymes are deficient, producing the characteristic clinical features?

• A Carbonic anhydrase, pyruvate carboxylase, and glutathione peroxidase
• B Ferritin and transferrin receptor for iron storage
• C Superoxide dismutase (SOD), ceruloplasmin, lysyl oxidase, dopamine-beta-hydroxylase, cytochrome c oxidase ✓
• D Molybdenum cofactor enzymes including sulfite oxidase

Explanation

ATP7A exports copper from enterocytes into the portal circulation for systemic distribution; its deficiency traps copper in enterocytes causing systemic copper deficiency despite normal gut intake. Deficient copper-dependent enzymes cause: (1) lysyl oxidase deficiency → impaired collagen/elastin crosslinking → connective tissue fragility, arterial aneurysms, 'kinky' steely hair; (2) dopamine-beta-hydroxylase deficiency → autonomic dysfunction; (3) cytochrome c oxidase deficiency → mitochondrial dysfunction/neurodegeneration; (4) ceruloplasmin deficiency → iron accumulation; (5) SOD deficiency → oxidative damage. This contrasts with Wilson disease (ATP7B mutation causing copper overload in liver/brain).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.