Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Ther Clin Risk Manag. 2012;8:373-6. doi: 10.2147/TCRM.S34954. Epub 2012 Aug 28.
Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene.
Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function.
Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder.
1 型原发性高草酸尿症（PH1）的特征是进行性肾功能不全，最终导致终末期肾病，以及与不同器官系统性草酸过多相关的广泛临床特征。它是由 AGXT 基因突变导致常染色体隐性遗传性丙氨酸：乙醛酸转氨酶缺乏引起的。
两名兄弟（一名 6 个月大；另一名 2 岁）分别因急性肾功能衰竭和尿路感染就诊。高尿草酸水平、骨活检中草酸晶体的显示以及致病性纯合已知 AGXT 基因突变证实了 PH1 的诊断。尽管具有相同的遗传背景、性别和共同的环境，但这两兄弟的结局却大不相同。其中一个因系统性草酸过多导致终末期肾病和多器官衰竭而较早死亡，而年龄较大的哥哥对吡哆醇有反应，发育和肾功能正常。
临床医生应该意识到 PH1 家族内的极端变异性，需要国际登记处来描述此类疾病的基因型-表型相关性。
