A serine-to-phenylalanine substitution leads to loss of alanine: glyoxylate aminotransferase catalytic activity and immunoreactivity in a patient with primary hyperoxaluria type 1

The lethal autosomal recessive disease primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT, EC 2.6.1.44). AGT is a homodimer of subunit molecular mass of 43 kDa and is encoded by a single gene located on chromosome 2q36-37 (HGMW-approved symbol for the AGT gene is AGXT). Several mutations of this gene have been identified in PH1 patients, each related to a specific enzymological phenotype, including peroxisome-to-mitochondrion AGT mistargeting, loss of AGT catalytic activity but maintenance of normally-targeted (i.e. peroxisomal) AGT immunoreactivity protein, and loss of both AGT catalytic activity and immunoreactivity. This paper reports the identification of a new mutation in the AGT gene in a PH1 patient who fits into the latter category.