A newborn screening panel detects elevated methionine in a 10-day-old infant. Further testing reveals homocysteine accumulation in blood and urine, lens dislocation, and skeletal abnormalities similar to Marfan syndrome. This condition is caused by deficiency of which enzyme in the methionine cycle?

• A Methionine adenosyltransferase
• B Methylenetetrahydrofolate reductase (MTHFR)
• C Cystathionine beta-synthase ✓
• D Homocysteine methyltransferase (methionine synthase)

Explanation

Classical homocystinuria is caused by cystathionine beta-synthase (CBS) deficiency, which catalyzes the condensation of homocysteine with serine to form cystathionine. CBS requires pyridoxal phosphate (vitamin B6). Accumulated homocysteine causes oxidative damage to collagen and fibrillin, leading to ectopia lentis, Marfanoid habitus, thromboembolism, and intellectual disability. Treatment includes B6 supplementation (in responsive cases), methionine restriction, and betaine.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.