Poyah Penelope, Bergman Joel, Geldenhuys Laurette, Wright Glenda, Walsh Noreen M, Hull Peter, Roche Kristina, West Michael L
Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Division of Nephrology, Nova Scotia Health Authority, Halifax, NS, Canada.
Can J Kidney Health Dis. 2021 Nov 22;8:20543581211058931. doi: 10.1177/20543581211058931. eCollection 2021.
Primary hyperoxaluria (PH) is a rare autosomal recessive disorder more commonly diagnosed in children or adolescents. Owing to its rarity and heterogeneous phenotype, it is often underrecognized, resulting in delayed diagnosis, including diagnosis after end-stage kidney disease (ESKD) has occurred or recurrence after kidney-only transplantation.
A 40-year-old Caucasian Canadian woman with a history of recurrent nephrolithiasis since age 19 presented with ESKD and cutaneous symptoms. She had no known prior kidney disease and no family history of kidney disease or nephrolithiasis.
A diagnosis of primary hyperoxaluria type 1 (PH1) due to homozygous splice donor mutation (AGXT c.680+1G>A) was made with kidney and cutaneous pathology demonstrating calcium oxalate deposition and ultrasound suggestive of nephrocalcinosis.
She was initiated on frequent, high-efficiency, high-flux conventional hemodialysis and oral pyridoxine. Lumasiran was added 11 months later, after she developed bilateral swan-neck deformities.
After 14 months of high-intensity dialysis and 3 months of lumasiran, there have been no signs of renal recovery, and extra-renal involvement has increased with progressive swan-neck deformities, reduced cardiac systolic function, and pulmonary hypertension. The patient has been waitlisted for kidney-liver transplantation.
This case report describes an adult presentation of PH1. The case highlights the importance of timely workup of metabolic causes of recurrent nephrolithiasis or nephrocalcinosis in adults which can be a presenting sign of PH and genetic testing for PH to facilitate early diagnosis and treatment especially in the era of novel therapeutics that may alter disease course and outcomes. The case also demonstrates the value of testing for PH in adults presenting with unexplained ESKD and a history of recurrent nephrolithiasis or nephrocalcinosis due to implications for organ transplantation strategy and presymptomatic family screening.
原发性高草酸尿症（PH）是一种罕见的常染色体隐性疾病，在儿童或青少年中更常被诊断出来。由于其罕见性和异质性表型，它常常未被充分认识，导致诊断延迟，包括在终末期肾病（ESKD）发生后才被诊断或仅进行肾脏移植后复发。
一名40岁的加拿大白人女性，自19岁起有复发性肾结石病史，现出现ESKD及皮肤症状。她既往无已知肾脏疾病，也无肾脏疾病或肾结石家族史。
因纯合剪接供体突变（AGXT c.680+1G>A）确诊为1型原发性高草酸尿症（PH1），肾脏和皮肤病理显示草酸钙沉积，超声提示肾钙质沉着症。
开始对她进行频繁、高效、高通量的常规血液透析及口服吡哆醇治疗。11个月后，在她出现双侧鹅颈畸形后加用鲁马西拉。
经过14个月的高强度透析及3个月的鲁马西拉治疗后，尚无肾脏恢复迹象，肾外受累情况有所增加，出现进行性鹅颈畸形、心脏收缩功能减退及肺动脉高压。该患者已被列入肝肾联合移植等待名单。
本病例报告描述了PH1在成人中的表现。该病例强调了对成人复发性肾结石或肾钙质沉着症的代谢病因进行及时检查的重要性，这可能是PH的一个表现体征，以及对PH进行基因检测以促进早期诊断和治疗的重要性，尤其是在可能改变疾病进程和结局的新型治疗方法的时代。该病例还证明了对出现不明原因ESKD且有复发性肾结石或肾钙质沉着症病史的成人进行PH检测的价值，因为这对器官移植策略和症状前家族筛查有影响。
