Hyperoxaluria by the AGXT gene: a case report

This report details a case of AGXT gene mutation in a male patient, 9 years 6 months old, Portuguese ethnicity, with history of nephrocalcinosis and recurrent nephrolithiasis in childhood, which progressed to chronic kidney disease. It illustrates the diagnostic and therapeutic implications of identifying an AGXT c.33dup (p.Lys12Glnfs156) variant in a patient with primary hyperoxaluria type 1. Recognizing nonresponsive genotypes prevents unnecessary prolonged treatment and allows earlier evaluation for advanced therapies such as liver transplantation or RNA interference therapy. A nine-year-old boy, white, with consanguineous parents and family history of early-onset end-stage renal disease, presented with recurrent nephrolithiasis and bilateral nephrocalcinosis since age 6 year. Initial evaluation revealed hyperoxaluria and elevated serum oxalate, confirming clinical suspicion of primary hyperoxaluria type 1 without pyridoxine response. At age 14 years, he developed acute renal failure due to obstructive urolithiasis and Acinetobacter baumannii infection, requiring ureteroscopic lithotripsy and intravenous antibiotics. Partial renal recovery followed, with stable function (estimated glomerular filtration rate ≈ 40 mL/min/1.73 m2) and no recurrence during longitudinal follow-up. At age 16 years, homozygosity for the primary hyperoxaluria type 1 gene, variant c.33dup (p.Lys12Glnfs*156), was identified, confirming primary hyperoxaluria type 1. Family screening revealed two asymptomatic siblings (ages 7 and 9 years) who were heterozygous carriers of the same variant. Lumasiran therapy was initiated for this patient as a disease-modifying treatment to reduce oxalate production and stabilize renal function. Primary hyperoxaluria type 1 remains a diagnostic and therapeutic challenge, particularly in resource-limited settings. Identification of specific AGXT variants offers key prognostic and therapeutic insights. Early genetic testing in children with unexplained nephrocalcinosis or recurrent nephrolithiasis may be cost-effective, enabling timely diagnosis, targeted treatment, and family screening while reducing the long-term burden and healthcare costs associated with end-stage renal disease. We present a case of primary hyperoxaluria type 1 due to AGXT mutation with familial involvement. Early genetic diagnosis and family screening are crucial, as broader access to testing can significantly improve outcomes in resource-limited settings.