Description of 5 Novel SLC34A3/NPT2c Mutations Causing Hereditary Hypophosphatemic Rickets With Hypercalciuria
Description of 5 Novel SLC34A3/NPT2c Mutations Causing Hereditary Hypophosphatemic Rickets With Hypercalciuria
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DOI：
10.1016/j.ekir.2019.05.004
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发表时间：
2019-08-01
影响因子：
6
通讯作者：
Bergwitz, Clemens
中科院分区：
文献类型：
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作者：
Chen, Alyssa;Ro, Hannah;Bergwitz, Clemens
遗传性低磷血症性佝偻病伴高钙尿症 (HHRH) 是一种罕见的常染色体隐性遗传病。该疾病被定位到 SLC34A3，即编码肾磷酸钠 (Pi) 协同转运蛋白 NPT2c 的基因。 1 低磷血症会导致成纤维细胞生长因子 23 (FGF23) 受到抑制、1, 25-二羟基维生素 D (1, 25 (OH) 2 D) 增加以及高钙尿症（HHRH 的标志），这与一组由 SLC34A1/NPT2a 2 功能丧失突变引起的 Pi 消耗性疾病所共有，但它与高钙尿症有所区别。 FGF23 依赖性低磷血症的 X 连锁和常染色体形式。 3 通常，具有纯合子或复合杂合子 SLC34A3/NPT2c 突变的患者在儿童时期就患有代谢性骨病，较少见的是肾结石和/或肾钙质沉着症。相反，杂合子携带者在生命后期会出现特发性高钙尿症，通常伴有轻度低磷血症和/或 1, 25 (OH) 2 D 水平升高，这将这种情况与其他形式的高钙尿症肾结石和/或肾钙质沉着症区别开来。 4 杂合子携带者通常不存在骨病。通过基因检测正确诊断 HHRH 对于及时治疗干预至关重要。在这里，我们描述了三名 HHRH 患者，我们在他们身上发现了五种新的复合杂合 SLC34A3/NPT2c 突变，并讨论了鉴别诊断和治疗策略。
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal-recessive disorder. The disease was mapped to SLC34A3, the gene encoding renal sodium-phosphate (Pi) cotransporter NPT2c. 1 Hypophosphatemia leads to suppression of fibroblast growth factor 23 (FGF23), increased 1, 25-dihydroxy vitamin D (1, 25 (OH) 2 D), and hypercalciuria, the hallmark of HHRH, which is shared by a group of Pi wasting disorders caused by loss-of-function mutations in SLC34A1/NPT2a 2 but differentiates it from X-linked and autosomal forms of FGF23-dependent hypophosphatemia. 3 Typically, patients with homozygous or compound heterozygous SLC34A3/NPT2c mutations present in childhood with metabolic bone disease and less commonly with nephrolithiasis and/or nephrocalcinosis. Conversely, heterozygous carriers present later in life with idiopathic hypercalciuria, often with mild hypophosphatemia and/or elevated 1, 25 (OH) 2 D levels, which set this condition apart from other forms of hypercalciuric nephrolithiasis and/or nephrocalcinosis. 4 Bone disease is generally absent in heterozygous carriers. Correct diagnosis of HHRH by genetic testing is essential for timely therapeutic intervention. Here we describe three individuals with HHRH in whom we discovered five novel compound heterozygous SLC34A3/NPT2c mutations, and discuss the differential diagnosis and treatment strategies.