A Case Report of Familial Primary Hyperoxaluria Type 1 Nephropathy with c.781C>G Gene Mutation and Literature Review

Primary hyperoxaluria type 1 (PH1), the most severe form of autosomal recessive hyperoxaluria, is caused by AGXT gene mutations that result in hepatic alanine-glyoxylate aminotransferase deficiency, which causes systemic oxalate accumulation and progressive nephropathy.

The study reported a unique AGXT c.781C>G mutation in a family with two PH1 patients; the mutation was not previously documented in the literature. A 19-year-old male (Patient 1) with a long history of nephrolithiasis presented with end-stage renal disease (ESRD), hyperoxaluria, and significant metabolic derangements, requiring renal replacement therapy (RRT). Genetic testing revealed a homozygous AGXT c.781C>G mutation, confirming the diagnosis of PH1. His parents both were heterozygous carriers of the same mutation, and the 46-year-old father (Patient 2) exhibited similar manifestations, including nephrolithiasis and chronic renal insufficiency, with progression to ESRD during follow-up. PH1 exhibits significant clinical and genotypic heterogeneity, ranging from asymptomatic cases to recurrent or occasional stone formation, nephrocalcinosis, and ESRD, often leading to missed or delayed diagnosis. Genetic testing is the gold standard. Early diagnosis allows for interventions such as hydration, pyridoxine therapy, RNAi treatments, or liver transplantation to slow renal function decline, while advanced cases may require RRT or combined liver-kidney transplantation.

This study firstly identified the AGXT c.781C>G mutation in PH1, expanding the known mutational spectrum of AGXT. The finding underscores the necessity of genetic screening in suspicious cases of familial nephrolithiasis or unexplained renal dysfunction.