Differential clinical characteristics of Chinese children with primary hyperoxaluria type 3

As a rare autosomal recessive disorder, primary hyperoxaluria type 3 (PH3) presents diagnostic challenges. Our comparative analysis of clinical characteristics between patients with PH3 and non-PH patients revealed distinct characteristics that may facilitate the diagnosis of PH3.

Clinical data from pediatric patients with urolithiasis who had undergone whole-exome sequencing from 2016-2024 were analyzed. Patients were divided into PH3 group and non-PH group on the basis of genetic testing.

Compared with non-PH patients, PH3 patients presented earlier onset (0.9 vs. 2.0 years, P = 0.021), higher incidence of nephrocalcinosis (22.22% vs. 3.17%, P = 0.008), higher serum calcium (2.55 vs. 2.49 mmol/L, P = 0.007), higher urinary oxalate levels (333.70 vs. 170.84 µg/mg, P = 0.008), higher urinary citrate levels (195.22 vs. 123.13 µg/mg, P = 0.015), lower urinary uric acid levels (838.44 vs. 1177.42 µg/mg, P = 0.040), and lower urinary calcium levels (113.27 vs. 352.21 µg/mg, P < 0.001). Subgroup analyses revealed that patients with PH3 had higher urinary oxalate levels (333.70 vs. 170.84 µg/mg, P = 0.042) than patients with cystinuria. Compared with patients in the other stone-related gene mutation groups, patients in the PH3 group presented earlier onset (0.9 vs. 2.5 years, P = 0.029), higher urinary oxalate levels (333.70 vs. 105.30 µg/mg, P = 0.045), higher urinary citrate levels (195.22 vs. 59.36 µg/mg, P < 0.001), and lower urinary calcium levels (113.27 vs. 421.24 µg/mg, P = 0.003). Patients with PH3 had greater incidence of nephrocalcinosis (22.22% vs. 0, P = 0.007), higher serum calcium levels (2.55 vs. 2.49 mmol/L, P = 0.030), higher urinary oxalate levels (333.70 vs. 182.74 µg/mg, P = 0.048) and lower urinary calcium levels (113.27 vs. 368.14 µg/mg, P = 0.004) than patients with negative molecular diagnoses.

Pediatric patients with PH3 are characterized by early onset, nephrocalcinosis, increased urinary oxalate excretion and lower urinary calcium excretion, which could provide guidance for earlier diagnosis of patients with PH3.