Valadares Luciana Pinto, de Carvalho Daniel Rocha
Unit of Osteometabolic Disorders, SARAH Network of Rehabilitation Hospitals, Brasília, Brazil.
Medical Genetics Unit, SARAH Network of Rehabilitation Hospitals, Brasília, Brazil.
J Clin Res Pediatr Endocrinol. 2023 Sep 8. doi: 10.4274/jcrpe.galenos.2023.2023-5-2.
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare FGF23-independent disorder caused by biallelic variants in the gene. The disease severity varies, and patients have an increased risk of developing renal complications. Phosphate supplementation is standard of care and active vitamin D analogs are not indicated as they could worsen the hypercalciuria. We report a Brazilian girl with HHRH who presented with knee pain and progressive genu valgum deformity that became apparent later in childhood (at age 8). Nephrocalcinosis was also identified at age 13. Next-generation sequencing (NGS) target panel directed to inherited forms of rickets detected compound heterozygous pathogenic variants in , including a novel missense variant c.1217G>T (p.Gly406Val). Compliance to oral phosphorus therapy was suboptimal and adjunctive chlorthalidone therapy improved hypercalciuria. Our case highlights the phenotypic variability of patients with HHRH and expands the growing list of variants associated with this disorder. An accurate diagnosis is crucial for proper treatment, and a thiazide diuretic may be useful as adjunctive therapy for controlling hypercalciuria.
遗传性低磷性佝偻病伴高钙尿症（HHRH）是一种由该基因双等位基因变异引起的罕见的不依赖成纤维细胞生长因子23（FGF23）的疾病。疾病严重程度各异，患者发生肾脏并发症的风险增加。补充磷是标准治疗方法，不建议使用活性维生素D类似物，因为它们可能会加重高钙尿症。我们报告了一名患有HHRH的巴西女孩，她出现膝关节疼痛和进行性膝外翻畸形，在儿童期较晚时（8岁）变得明显。13岁时还发现了肾钙质沉着症。针对遗传性佝偻病形式的下一代测序（NGS）靶向 panel检测到该基因中的复合杂合致病性变异，包括一个新的错义变异c.1217G>T（p.Gly406Val）。口服磷治疗的依从性欠佳，辅助使用氯噻酮治疗改善了高钙尿症。我们的病例突出了HHRH患者的表型变异性，并扩大了与该疾病相关的该基因变异的不断增加的列表。准确诊断对于恰当治疗至关重要，噻嗪类利尿剂可能作为控制高钙尿症的辅助治疗有用。
