Background

Three types of primary hyperoxaluria (PH) are recognized. However, data on PH type 2 (PH2), caused by defects in the GRHPR gene, are limited.

Methods

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.

Results

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 m²/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.

Conclusions

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.

Graphical abstract

中文翻译：

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2 型原发性高草酸尿症儿童的临床特征、遗传特征和短期结局：全国经验

背景

已知三种类型的原发性高草酸尿症 (PH)。然而，由GRHPR基因缺陷引起的 2 型 PH (PH2) 的数据有限。

方法

我们回顾了来自印度七个中心的 18 岁以下经基因证明的 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，并确定基因型与表型之间是否存在相关性。存在。

结果

我们报告了 20 名患者（均患有肾结石或肾钙质沉着症），其中位 (IQR) 年龄为 21.5 (7, 60) 个月，被诊断患有 PH2。分别有 9 名 (45%) 和 8 名 (40%) 患者有肾结石的近亲和家族史。PH2 诊断时的中位血清肌酐 (IQR) 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 2 / ^min。在 12 名 (60%) 患者中发现了白种人中罕见的突变热点 (c.494 G > A)。在五名 (25%) 患者中发现内含子剪接位点变异 (c.735-1G > A)。四名 (20%) 患者需要手术干预来取出结石。在 12 (6, 27) 个月的中位 (IQR) 随访中，有 6 名 (30%) 患者出现了主要肾脏不良事件（死亡或慢性肾脏病 (CKD) 3-5 期）。无法确定 CKD 进展的危险因素和基因型-表型相关性。

结论

PH2 不应再被视为一种无害疾病，而应被视为一种潜在的侵袭性疾病，发病年龄较早，并且某些患者可能在儿童时期迅速进展至 CKD 3-5 期。在 60% 的病例中发现了突变热点（c.494 G > A 变体），但需要进一步探索以破译基因型与表型的相关性。

图形概要