Primary Hyperoxaluria Type 2 Masquerading as Chronic Kidney Disease of Unknown Origin in an Adolescent: A Case Report

Primary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism characterized by hepatic overproduction of oxalate, leading to oxalate nephropathy and systemic oxalosis without early intervention. PH1 contributes to 80% of the cases, while PH2 (10%) and PH3 (10%) being relatively rarer. PH carries a prevalence of one to three per one million population, and PH2 (pathogenic GRHPR gene variant) exhibits high phenotypic heterogeneity, complicating its diagnosis. We present a 17-year-old male who presented with a subacute onset of fever, dyspnea, oliguria, and volume overload for two weeks. Laboratory findings revealed: hemoglobin 5.2 g/dL, urea 194 mg/dL, creatinine 10.6 mg/dL, calcium 5.8 mg/dL, albumin 3.8 g/dL, and bicarbonate 12 mmol/L. Urinalysis showed 10-12 pus cells with significant proteinuria (2256 mg/day). Blood pressure was persistently elevated during hospitalization, and ultrasound revealed small kidneys (right 8.7 × 3.5 cm, left 8.3 × 4.1 cm). Evaluation for secondary causes of hypertension and chronic kidney disease (CKD) in the young patients was unremarkable; however, imaging studies identified nephrocalcinosis and urinalysis confirmed hyperoxaluria (96 mg/day) with elevated plasma oxalate levels (93 μmol/L). Secondary hyperoxaluria was excluded, and genetic analysis for PH confirmed a homozygous missense mutation (c.349T>C) in exon 4 of the GRHPR gene. High suspicion, accurate diagnosis, and timely interventions are mandatory to halt the progression of the disease in PH2. Management remains challenging, often necessitating intensive dialysis and consideration for either isolated kidney or combined liver-kidney transplantation as the definitive cure, with novel therapies such as RNA interference agents currently under investigation.