A 36-year-old man with intellectual disability is referred to a vascular surgeon due to the presence of severe popliteal artery plaques. On physical examination, the patient is noted to have above average height, and an eye exam reveals downward lens dislocation. Laboratory tests reveal elevated methionine and homocysteine levels.
In which of the following is the patient most likely deficient?
- A) Cystathionine synthase
- B) Homocysteine methyltransferase
- C) Methionine synthase
- D) Vitamin B9
- E) Vitamin B12
A) Cystathionine synthase
This patient has congenital homocystinuria evidenced by the classic signs of tall habitus, downward lens dislocation, and intellectual disability. To determine the answer, the pathway of homocysteine and methionine metabolism must be known. The only answer that will raise BOTH methionine and homocysteine levels is cystathionine synthase, an enzyme that catalyzes the first step of the transculturation pathway, from homocysteine to cystathionine, which is subsequently converted to cysteine.
Answers choices B, C, D, and E, are incorrect. Each of these choices would result in a decrease in methionine levels.
Key Learning Point
A tall patient with a Marfan-like figure and downward lens dislocation who has atherosclerosis is indicative of a patient suffering from congenital homocystinuria. When both homocysteine and methionine levels are elevated, a cystathionine synthase deficiency is present.