ExtractLiver biopsy specimens from four patients with homocystinuria were examined by electron microscopy before and after treatment with massive doses of pyridoxine. The chief abnormalities found were as follows: unusually shaped mitochondria, hypertrophy of the smooth endoplasmic reticulum, and numerous pericanalicular lysosomes.Several of the mitochondria in each cell in the various zones of the liver lobule had narrow projections and breaks in the outer mitochondrial membrane. Mitochondria were normal in size, but the mitochondrial dark granules appeared larger than normal.Two patients responded biochemically to treatment by disappearance of hyper-methioninemia and homocystinemia. No recognizable differences in hepatocellular structure resulted from treatment in any of the patients.SpeculationPatients with homocystinuria who respond to pyridoxine treatment by disappearance of hypermethioninemia and homocystinemia exhibit no change in ultrastructural aberrations following treatment. This suggests that “toxic” accumulation of metabolites proximal to an enzymatic block may not account for all the phenotypical manifestations of inborn errors of the metabolism of amino acids.