Abstract
BackgroundPrimary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis.MethodsTwo unrelated patients with recurrent urolithiasis, along with members of their families, exhibited mutations in the AGXT gene by PCR direct sequencing.ResultsTwo heterozygous mutations that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in one patient. The p.S81X mutation is novel. Two heterozygous missense mutations, p.M1T and p.I202N, were detected in another patient but were not identified in her sibling. These four mutations were confirmed to be of paternal and maternal origin.ConclusionsThese are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China. The novel p.S81X and p.I202N mutations detected in our study extend the spectrum of known AGXT gene mutations.
Highlights
Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis
Primary hyperoxaluria type 1 (PH1; MIM# 259900) is an autosomal recessive disorder of glyoxylate metabolism, leading to the overproduction of endogenous oxalate; patients present with urolithiasis and/or nephrocalcinosis [1,2]
The disease is caused by mutations in the AGXT gene (MIM#604285), which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyses the transamination of glyoxylate to glycine [3,4]
Summary
Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Primary hyperoxaluria type 1 (PH1; MIM# 259900) is an autosomal recessive disorder of glyoxylate metabolism, leading to the overproduction of endogenous oxalate; patients present with urolithiasis and/or nephrocalcinosis [1,2]. The disease is caused by mutations in the AGXT gene (MIM#604285), which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyses the transamination of glyoxylate to glycine [3,4]. A few sporadic cases of PH1 have been reported in mainland China, mutational analysis of AGXT was not performed in these cases. We hope that the presentation of rare cases will contribute to understanding the spectrum of the disease by aiding its clinical identification and pathogenetic understanding
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