Supplementary Material for: Variable Clinical Presentation of Children with Hereditary Hypophosphatemic Rickets with Hypercalciuria: A Case Series and Review of the Literature

Introduction: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a rare condition of renal phosphate wasting due to SLC34A3 mutations [1]. Patients exhibit low serum phosphorus, high 1,25-dihydroxyvitamin D and inappropriately high urine phosphate and calcium. However, symptoms vary and little is known about specific phenotype-genotype correlations. Methods: We report three HHRH cases in unrelated 12-year-old, 9-year-old and 14-year-old patients and perform a systematic literature review. Results: All three patients exhibited labs typical of HHRH. Yet, their presentations differed and 2 novel SLC34A3 variants were identified. As found in the literature review, bone symptoms are most common (50%), followed by renal symptoms (17%), combined bone and renal symptoms (18%) and asymptomatic (9%). Conclusion: These three cases highlight the variability of presenting signs and symptoms among individuals with HHRH. An accurate diagnosis is critical, as treatment differs from other disorders of phosphate wasting, urinary stones, and mineralization defects.

引言：遗传性低血磷性佝偻病伴高钙尿症（Hereditary Hypophosphatemic Rickets with Hypercalciuria，HHRH）是一种因SLC34A3基因突变导致的罕见肾性失磷疾病[1]。患者表现为血清磷水平降低、1,25-二羟维生素D水平升高，以及尿液中磷和钙水平异常升高。然而，该疾病的临床症状存在异质性，目前对其特定表型-基因型关联的认知仍十分有限。
方法：本研究报道3例无亲缘关系的HHRH患者，年龄分别为12岁、9岁和14岁，并开展了系统性文献回顾。
结果：3例患者的实验室检查结果均符合HHRH的典型特征，但各自的临床表现存在差异，且共鉴定出2个全新的SLC34A3基因变异。结合本次文献回顾结果，骨骼症状最为常见（占比50%），其次为肾性症状（17%）、骨骼与肾性联合症状（18%），以及无症状病例（9%）。
结论：本研究的3例病例凸显了HHRH患者临床表现的异质性。由于其治疗方案与其他肾性失磷疾病、尿路结石及骨矿化缺陷类疾病存在差异，因此精准诊断对该疾病而言至关重要。