Abstract：
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of phosphate homeostasis. We describe a single-center experience of genetically proven HHRH families and perform systematic review phenotype-genotype correlation in reported biallelic probands and their monoallelic relatives. Detailed clinical, biochemical, radiological, and genetic data were retrieved from our center and a systematic review of Pub-Med and Embase databases for patients and relatives who were genetically proven. Total of nine subjects (probands:5) carrying biallelic SLC34A3 mutations (novel:2) from our center had a spectrum from rickets/osteomalacia to normal BMD, with hypophosphatemia and hypercalciuria in all. We describe the first case of genetically proven HHRH with enthesopathy. Elevated FGF23 in another patient with hypophosphatemia, iron deficiency anemia, and noncirrhotic periportal fibrosis led to initial misdiagnosis as tumoral osteomalacia. On systematic review of 58 probands (with biallelic SLC34A3 mutations; 35 males), early-onset HHRH and renal calcification were present in ~ 70% and late-onset HHRH in 10%. c.575C > T p.(Ser192Leu) variant occurred in 53% of probands without skeletal involvement. Among 110 relatives harboring monoallelic SLC34A3 mutation at median age 38 years, renal calcification, hypophosphatemia, high 1,25(OH)2D, and hypercalciuria were observed in ~30%, 22.3%, 40%, and 38.8%, respectively. Renal calcifications correlated with age but were similar across truncating and non-truncating variants. Although most relatives were asymptomatic for bone involvement, 6/12(50%) had low bone mineral density. We describe the first monocentric HHRH case series from India with varied phenotypes. In a systematic review, frequent renal calcifications and low BMD in relatives with monoallelic variants (HHRH trait) merit identification.
摘要：
遗传性高钙尿症（HHRH）的低磷血症病是一种罕见的磷酸盐稳态疾病。我们描述了经过遗传证明的HHRH家族的单中心经验，并在报告的双等位基因先证者及其单等位基因亲属中进行了系统的表型-基因型相关性评价。详细的临床，生物化学，放射学,我们从我们的中心检索了遗传数据,并对Pub-Med和Embase数据库进行了系统评价,这些数据库适用于经过遗传证明的患者和亲属.来自我们中心的携带双等位基因SLC34A3突变（新颖：2）的共有9名受试者（先证者：5）具有从of病/骨软化症到正常BMD的频谱，伴有低磷酸盐血症和高钙尿症。我们描述了第一例经遗传证实的HHRH伴附着点病。另一名低磷酸盐血症患者的FGF23升高，缺铁性贫血,非肝硬化门静脉周围纤维化导致最初误诊为肿瘤骨软化症。对58位先证者（具有双等位基因SLC34A3突变；35位男性）进行了系统评价，早发性HHRH和肾钙化的发生率约为70％，晚发性HHRH的发生率约为10％。c.575C>Tp。（Ser192Leu）变异发生在53％的先证者中，没有骨骼受累。在中位年龄38岁的110位具有单等位基因SLC34A3突变的亲属中，肾钙化,低磷酸盐血症,高1,25(OH)2D，高钙尿症观察到~30%，22.3%,40%,38.8%,分别。肾脏钙化与年龄相关，但在截断和非截断变体中相似。尽管大多数亲属无症状的骨受累，6/12(50%)骨密度低。我们描述了来自印度的第一个单中心HHRH病例系列，具有不同的表型。在系统审查中，具有单等位基因变异（HHRH性状）的亲属中频繁的肾脏钙化和低BMD值得鉴定。
