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.

遗传性低磷血症性佝偻病伴高钙尿症 (HHRH) 是一种罕见的磷酸盐稳态紊乱。我们描述了基因证明的 HHRH 家族的单中心经验，并对报告的双等位基因先证者及其单等位基因亲属进行了系统回顾表型-基因型相关性。从我们的中心检索了详细的临床、生化、放射学和遗传数据，并对经过基因验证的患者和亲属的 Pub-Med 和 Embase 数据库进行了系统审查。来自我们中心的总共 9 名携带双等位基因SLC34A3突变（新颖：2）的受试者（先证者：5）患有从佝偻病/骨软化症到正常 BMD 的谱系，全部患有低磷血症和高钙尿症。我们描述了第一例经基因证实的 HHRH 伴有附着点病的病例。另一名患有低磷血症、缺铁性贫血和非肝硬化门静脉周围纤维化的患者的 FGF23 升高导致最初被误诊为肿瘤性骨软化症。对 58 名先证者（具有双等位基因SLC34A3突变；35 名男性）的系统回顾显示，约 70% 存在早发性 HHRH 和肾钙化，10% 存在晚发性 HHRH。c.575C > T p.(Ser192Leu) 变异发生在 53% 的先证者中，但没有骨骼受累。在 110 名中位年龄为 38 岁、携带单等位基因SLC34A3突变的亲属中，观察到肾钙化、低磷血症、高 1,25(OH) ₂ D 和高钙尿症的比例分别约为 30%、22.3%、40% 和 38.8%。肾钙化与年龄相关，但截短型和非截短型的肾钙化相似。尽管大多数亲属没有骨受累症状，但 6/12（50%）的骨密度较低。我们描述了来自印度的第一个具有不同表型的单中心 HHRH 病例系列。在一项系统评价中，具有单等位基因变异（HHRH 特征）的亲属中频繁的肾钙化和低 BMD 值得鉴定。