Diversity in residual alanine glyoxylate aminotransferase activity in hyperoxaluria type I: Correlation with pyridoxine responsiveness

Primary hyperoxaluria type I is a rare genetic disorder of glyoxylate metabolism in which patients usually present during the first decade of life with recurrent calcium oxalate nephrolithiasis (see Williams and Smith, 1983). Although it was long believed that hyperoxaluria type I is associated with a deficiency of the cytosolic form of 2-oxoglutarate: glyoxylate carboligase, it is now clear that the primary defect in hyperoxaluria type I is at the level of a deficient alanine: glyoxylate aminotransferase activity as first shown by Danpure and Jennings (1986). Although most hyperoxaluria type I patients die before 20 years of age from progressive renal insufficiency, several patients have been described suffering from a milder, pyridoxine responsive form of hyperoxaluria type I (see Williams and Smith, 1983). In these patients the urinary excretion of oxalate and glycolate, the two characteristic metabolites in blood and urine from hyperoxaluria type I patients, can be reduced upon administration of pyridoxine. In the present report we determined the activity of alanine glyoxylate aminotransferase (AGT) in liver needle specimens from one patient who died from pyridoxine-resistant hyperoxaluria type I and three patients with the pyridoxine-responsive form of the disease using an improved sensitive enzyme assay.