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Section XV - Homocysteine Metabolism

I. Homocystinuria (Figure 2.5.17)

A. Most commonly due to a deficiency of
cystathionine synthase
B. ↑ homocysteine in urine
C. Cysteine becomes an essential amino acid
D. Symptoms include intellectual disability,
hypercoagulability, ectopia lentis (lens
displacement), and a marfanoid habitus.

II. Vitamin B12 (cobalamin)

A. Necessary for the conversion of homocysteine
→ methionine and methylmalonyl-CoA →
succinyl-CoA
B. Deficiency results in ↑ methylmalonic acid
(MMA) and homocysteine

III. Vitamin B9 (folate)

A. Necessary for the conversion of homocysteine
→ methionine
B. Deficiency results in ↑ homocysteine and
normal levels of MMA

Figure 2.5.18 - Homocysteine metabolism

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REVIEW QUESTIONS
1. A 4-year-old boy is brought to the physician
by his mother due to swelling in his leg. The
mother states that his symptoms developed
yesterday. Since then the boy has complained
of difficulty walking. On exam he is noted to
be intellectually delayed. He is in the 99th
percentile for height and his limbs are especially
elongated. Labs reveal elevated cystathionine
and homocysteine. A deficiency of what enzyme
is most likely responsible for this patient’s
condition?
• Marfanoid habitus (elongated limbs),
intellectual disability, DVTs, and elevated
cystathionine and homocysteine → homo-
cystinuria
• Elevated cystathionine and homocysteine →
deficiency of methionine synthase
?
2. A homeless male presents to the ED with a
constellation of symptoms and the physician
on call is concerned about a vitamin deficiency.
Labs are ordered and reveal elevated levels
of homocysteine and normal levels of
methylmalonic acid. Supplementation with
what vitamin would likely improve this patient’s
condition?
• ↑ homocysteine and normal levels of meth-
ylmalonic acid → folate deficiency (supple-
mentation with folate would improve this
patient’s condition)