Pediatric Nephrology Services, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India.
Department of Pediatric Nephrology, St John's Medical College Hospital, Bangalore, India.
Pediatr Nephrol. 2024 Apr;39(4):1093-1104. doi: 10.1007/s00467-023-06200-9. Epub 2023 Nov 2.
Three types of primary hyperoxaluria (PH) are recognized. However, data on PH type 2 (PH2), caused by defects in the GRHPR gene, are limited.
We reviewed the medical records of patients < 18 years of age with genetically-proven PH2 from seven centres across India to identify the age of onset, patterns of clinical presentation, short-term outcomes and genetic profile, and to determine if genotype-phenotype correlation exists.
We report 20 patients (all with nephrolithiasis or nephrocalcinosis) diagnosed to have PH2 at a median (IQR) age of 21.5 (7, 60) months. Consanguinity and family history of kidney stones were elicited in nine (45%) and eight (40%) patients, respectively. The median (IQR) serum creatinine at PH2 diagnosis was 0.45 (0.29, 0.56) mg/dL with the corresponding estimated glomerular filtration rate being 83 (60, 96) mL/1.73 m/min. A mutational hotspot (c.494 G > A), rare in Caucasians, was identified in 12 (60%) patients. An intronic splice site variant (c.735-1G > A) was noted in five (25%) patients. Four (20%) patients required surgical intervention for stone removal. Major adverse kidney events (mortality or chronic kidney disease (CKD) stages 3-5) were noted in six (30%) patients at a median (IQR) follow-up of 12 (6, 27) months. Risk factors for CKD progression and genotype-phenotype correlation could not be established.
PH2 should no longer be considered an innocuous disease, but rather a potentially aggressive disease with early age of presentation, and possible rapid progression to CKD stages 3-5 in childhood in some patients. A mutational hotspot (c.494 G > A variant) was identified in 60% of cases, but needs further exploration to decipher the genotype-phenotype correlation.
原发性高草酸尿症（PH）有三种类型。然而，关于由 GRHPR 基因突变引起的 PH2 的数据有限。
我们回顾了来自印度七个中心的年龄<18 岁的经基因证实的 PH2 患者的病历，以确定发病年龄、临床表现模式、短期结果和遗传特征，并确定是否存在基因型-表型相关性。
我们报告了 20 名患者（均患有肾结石或肾钙质沉着症），在中位数（IQR）年龄 21.5（7，60）个月时被诊断为 PH2。在 9 名（45%）和 8 名（40%）患者中分别发现了近亲结婚和肾结石家族史。在 PH2 诊断时，中位数（IQR）血清肌酐为 0.45（0.29，0.56）mg/dL，相应的估计肾小球滤过率为 83（60，96）mL/1.73 m/min。在 12 名（60%）患者中发现了一个突变热点（c.494 G > A），在白种人中罕见。在 5 名（25%）患者中发现了一个内含子剪接位点变异（c.735-1G > A）。有 4 名（20%）患者需要手术取石。在中位数（IQR）随访 12（6，27）个月时，有 6 名（30%）患者发生主要不良肾脏事件（死亡或慢性肾脏病（CKD）3-5 期）。CKD 进展的危险因素和基因型-表型相关性无法确定。
PH2 不应再被视为一种无害的疾病，而应被视为一种潜在的侵袭性疾病，在某些患者中，其发病年龄较早，且可能在儿童期迅速进展至 CKD 3-5 期。在 60%的病例中发现了一个突变热点（c.494 G > A 变异），但需要进一步探索以阐明基因型-表型相关性。
