Nine novel HOGA1 gene mutations identified in primary hyperoxaluria type 3 and distinct clinical and biochemical characteristics in Chinese children

Background Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are thought to present with a less severe phenotype than PH1 and PH2 patients. However, the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aims of this study were to report HOGA1 mutations of PH3 in Chinese children, and to analyze the genotype and clinical characteristics of these PH3 patients. Methods Genetic analysis (targeted gene panel-based and/or whole-exome sequencing) of HOGA1 was performed in 52 patients with a high suspicion of PH3, and DNAwas obtained from the patient and both the parents. The clinical, biochemical, and genetic data of these 12 patients identified with HOGA1 mutations were subsequently retrospectively reviewed. Results These 12 patients were identified with HOGA1 mutation. The median onset of clinical symptoms was 18.25 (range 538) months. In total, 14 different mutations were identified including 9 novel mutations in these 12 patients with PH3. All of these 12 patients initially presented with urolithiasis, and 3 patients among them comorbid urinary tract infection (UTI) as another initial symptom. Ten patients experienced hyperoxaluria (average oxalate 0.77 mmol/1.73 m(2)/24h). In contrast, urine calcium excretion was normal in 8 patients and 2 patients with hypercalciuria (urine calcium > 4mg/kg/24 h). At the time of diagnosis, estimated GFR was 155.6 ml/min per 1.73 m(2), and at last follow-up time (17.3 months later from diagnosis on average), estimated GFR was 157.5 ml/min per 1.73 m(2). To date, none of the patients has impaired renal function based on and progressed to ESRD. Conclusions We found that PH3 was significantly diagnosed in our urolithiasis patients during childhood. Nine novel HOGA1 mutations were identified in association with PH3, which provide a first-line investigation in Chinese PH3 patients. The eGFR was normal in all children with PH3. This finding is in contrast to the early impairment of renal function in PH1 and PH2.