Pyridoxine treatment does not prevent homocystinemia after methionine loading in adult homocystinuria patients

Abstract

Fasting homocystinemia in homocystinuria due to cystathionine synthase deficiency reportedly disappears on high-dose pyridoxine treatment. This does not necessarily reflect normal tolerance to methionine. The present study compares the effects of oral methionine loading on homocystine, cystine, and homocysteine-cysteine disulphide profiles in 8 adult homozygous homocystinuria patients on and off pyridoxine treatment and in 20 controls. Pyridoxine nearly normalized fasting serum amino acid levels. Nevertheless, with a similar methionine load the patient's homocystine levels on and off treatment rose and the cystine levels decreased, reflecting the ongoing formation of the homocysteine-cysteine disulphide in the presence of impaired transsulphuration of homocysteine. In the controls homocystinemia remained virtually absent and cystine transiently rose which indicates normal transsulphuration. On treatment methionine loading evoked a brisk rise of the homocysteine-cysteine disulphide levels to values equal to those off treatment, when these levels virtually plateaued after the load. Thus, pyridoxine treatment attenuates the biochemical abnormalities in the fasting patients but leaves their impaired capacity to handle major methionine loads essentially unchanged.