Preliminary report: hyperhomocysteinemia in patients with acute intermittent porphyria.

Homocysteine is an intermediate of methionine metabolism, and its elevation in tissues is correlated with an increased risk for vascular diseases. We measured homocysteine in plasma of 24 patients with acute intermittent porphyria (AIP) and long-term high excretion of heme precursors. Fifteen (62.5%) presented hyperhomocysteinemia (total homocysteine in plasma >15 μmol/L). No association was found between hyperhomocysteinemia and either urinary excretion of heme precursors or clinical status. All the patients showed normal levels of vitamin B₁₂ and folic acid, but 13 (54%) presented low plasma levels of pyridoxal 5'-phosphate (PLP <15 nmol/L). Cystathionine β-synthase (CBS) catalyzes a major removal pathway of homocysteine and is dependent on both PLP and heme as cofactors. It is hypothesized that, in AIP, CBS reduced hepatic activity resulting from either a low heme status and/or consumptive depletion of PLP due to increased demand by 5-aminolevulinatesynthase hyperactivity can induce hyperhomocysteinemia.