PH has autosomal recessive inheritance. Three genetic mutations have been identified:
- Type 1: glyoxylate aminotransferase (80% of cases)
- Type 2: mutation in gene for glyoxylate reductase / hydroxypyruvate reductase enzyme (10% of cases)
- Type 3: HOGA1 gene mutation (approximately 5% of cases)
Most patients are diagnosed as neonates during routine metabolic screening, which will reveal increased oxalate excretion in the urine. If not detected on neonatal screening, some patients will present with oxalate nephrolithiasis, nephrocalcinosis with or without renal injury, or hyperoxaluria with no underlying chronic gastrointestinal disease. Those with nephrocalcinosis may present with recurrent urinary tract infections. Oxalate deposition can vary widely among individual patients, leading to a varied clinical presentation at different ages. In general, approximately 50% of patients with PH type 1 present with renal symptoms by early adulthood, and PH type 2 presents later in life, but both patient populations develop end-stage renal disease. PH type 3 most commonly presents in early childhood but rarely develops end-stage renal failure.