Primary Hyperoxaluria Type 1: A Case Report

Background: Primary Hyperoxaluria type 1 (PH1) is a rare autosomal recessive inherited disease, with an estimated incidence of 1:100 000 live births per year in Europe. It is caused by mutations in AGXT gene, leading to liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT) dysfunction. Its heterogeneous presentation proves a diagnostic challenge and a high level of suspicion is necessary for an early diagnosis. Over 50% already present with end stage renal disease (ESRD) at time of diagnosis.

Case report: We report the case of a 14-year-old boy, second child to consanguineous parents, followed in Pediatric Nephrology consultation of a tertiary hospital. No relevant past history, except for enuresis and minor beta-talassemia. He was first referred at the age of 9 for recurrent lithiasis (episodes of stone elimination) and ureteral dilatation. At presentation, estimated glomerular filtration rate (eGFR) was 32.3 mL/min/1.73m² and ultrassonography (US) confirmed bilateral renal lithiasis causing right ureter obstruction and nonspecific parenchymal hyperechogenicity. Stone analysis revealed calcium oxalate monohydrate crystals and 24-h urine had markedly elevated urine oxalate excretion (2.22 mmol/1.73m²/day). Besides hydration, he was treated with sodium and potassium citrate and pyridoxine, and eGFR transiently improved (93.7 mL/min/1.73m²). However, despite increasing doses, urine oxalate excretion remained more than 3-fold higher than reference values. Genetic tests confirmed a mutation in AGXT gene, c.1151T>C, in homozygosity. Approximately two years after initial symptoms, nephrocalcinosis was identified in US, consistent with the diagnosis, and eGFR gradually declined while albuminuria and uricemia got elevated. Oxalate deposition in myocardium, retina, bone marrow and thyroid was excluded following a multidisciplinary approach. At 14 years old, eGFR went bellow 40 mL/min/1.73m² and he was then proposed for a sequential liver-kidney transplantation. Liver transplantation of deceased donor was performed with no major complications.

Conclusions: Recurrent urolithiasis and nephrocalcinosis in children along with suggestive family history/consanguinity should raise the suspicion of PH1. Definite diagnosis is based on mutation analysis. Conservative treatment may increase renal survival, therefore it should be started when the disease is first suspected. Sequential or combined liver and kidney transplantation should be planned when eGFR declines below 40mL/min/1.73m² to avoid systemic complications of systemic oxalosis.