Which metabolic disorder involves accumulation of homocysteine, leading to vascular thrombosis and behavioral disturbances, treated with vitamin B6?

• A. Prader-Willi syndrome
• B. Angelman syndrome
• C. Homocystinuria
• D. Velocardiofacial syndrome

Answer: (C)

Elevated homocysteine with vascular thrombosis and behavioral disturbances points to homocystinuria, a metabolic disorder of sulfur-containing amino acid metabolism. In the classic form, a deficiency of cystathionine beta-synthase prevents homocysteine from being converted to cystathionine, causing homocysteine to accumulate. Vitamin B6 (pyridoxine) serves as a cofactor for the CBS enzyme, so high-dose B6 can enhance residual enzyme activity in some patients and lower homocysteine levels, reducing the risk of thrombosis and the neurodevelopmental issues that can accompany the condition. Clinically, this disorder often presents with a marfanoid habitus, downward lens subluxation, osteoporosis, and premature vascular events, along with developmental or behavioral disturbances.

The other conditions listed are not metabolic disorders of homocysteine metabolism and do not characteristically involve vascular thrombosis due to homocysteine accumulation or respond to B6 in this way. Prader-Willi and Angelman syndromes are neurodevelopmental disorders arising from imprinted genes on chromosome 15 with distinct clinical features. Velocardiofacial syndrome (22q11.2 deletion) involves congenital heart defects, palatal abnormalities, and learning difficulties, not a primary homocysteine metabolism problem.