Hyperhomocysteinemia in acute hepatic porphyria (AHP) and implications for treatment with givosiran.

The strong correlation and co-increase of homocysteine and methionine suggest that HHcy associated with givosiran is likely attributable to the impaired trans-sulfuration pathway catalyzed by cystathionine β-synthase, which uses vitamin B6 as a cofactor. Data-based consensus supports monitoring total plasma homocysteine and vitamin B6, B12, and folate levels before and during givosiran treatment; supplementing with pyridoxine/vitamin B6 in patients with homocysteine levels >100 μmol/L; and involving patients with homocysteine levels >30 μmol/L in decisions to supplement.