In Homocystinuria, deficiency of which enzyme?

• A. Cystathione Beta-Synthase
• B. Methionine Adenosyltransferase
• C. Homocysteine Methyltransferase
• D. Phenylalanine Hydroxylase

Answer: (A)

Cystathione beta-synthase is the enzyme at the heart of this condition. It catalyzes the first step in the transsulfuration pathway, converting homocysteine and serine into cystathionine. When this enzyme is deficient, homocysteine cannot be degraded further, so it accumulates in the blood and urine. As a consequence, methionine levels often rise because excess homocysteine is diverted into the methionine remethylation pathway. Clinically, this leads to homocystinuria with features such as lens subluxation, marfanoid habitus, thromboembolic events, and possible cognitive issues. Treatments focus on lowering homocysteine, sometimes with pyridoxine (vitamin B6) if the patient is responsive, and may include dietary methionine restriction and B12/folate support depending on the specific defect in the remethylation pathway. The other enzymes listed are involved in related steps (remethylation or methylation) or in unrelated pathways and do not explain the classic presentation of homocystinuria due to CBS deficiency.