HOGA1 HOGA1 Gene Mutations of Primary Hyperoxaluria Type 3 in Tunisian Patients

摘要

Background Primary hyperoxaluria type 3 ( PH 3) is due to mutations in the recently identified 4‐hydroxy‐2‐oxoglutarate aldolase ( HOGA 1 ) gene. PH 3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. The aim of this study was to report three PH 3 cases carrying mutations in HOGA 1 . Materials and Methods Genetic analysis of HOGA 1 was performed in patients with a high clinical suspicion of PH after sequencing of AGXT and GRHPR genes, which was negative. Also, a complete AGXT / GRHPR MLPA was performed in these patients in order to detect large deletions/insertions. Results and Discussion Two different HOGA 1 gene mutations were identified: the p.Pro190Leu in a homozygous state and the p.Gly287Val in two patients in homozygous and heterozygous carriers. The median age at onset of clinical symptoms was 3.93 years. Most of the patients had a positive family history for recurrent urolithiasis. The p.Pro190Leu mutation was reported with impaired renal function at follow‐up; however, the p.Gly287Val was presented with normal renal function. All patients were presented with urolithiasis, but only one had a nephrocalcinosis. Conclusion This study expanded the number of PH 3 patients from 63 to 66 cases. The p.Pro190Leu and the p.Gly287Val mutations found in this study can provide a first‐line investigation in Tunisian PH 1 patients.