Department of Pediatrics, V. Buzzi Children's Hospital, Università di Milano, Via Lodovico Castelvetro, 32, 20154 Milan, Italy.
Clinical Genetics Service, V. Buzzi Children's Hospital, Università di Milano, Via Lodovico Castelvetro, 32, 20154 Milan, Italy.
Int J Environ Res Public Health. 2021 Aug 19;18(16):8771. doi: 10.3390/ijerph18168771.
Autosomal dominant hypophosphatemic rickets (ADHR) is an extremely rare form of genetic rickets caused by mutations in the fibroblast growth factor 23 gene. ADHR is characterized by hypophosphatemia secondary to isolated renal phosphate wasting. Only a few cases of ADHR have been reported in the literature to date. We describe the case of a 17-month-old girl who presented with severe failure to thrive (length: -4.08 standard deviation (SD), weight: -2.2 SD) and hypotonia. Hypophosphatemia, decreased tubular phosphate reabsorption (69%), and rachitic lesions were found. Genetic analysis showed the heterozygous variant c.536G>A (NM_020638.3:c.536G>A) in exon 3 of the FGF23 gene, leading to the diagnosis of ADHR. She was treated with phosphate salts and oral alfacalcidol. After 4 years of treatment, at 5 years of age, the patient's ADHR resolved spontaneously. Considering the lack of knowledge regarding ADHR, we reviewed the literature to describe the features of this rare and poorly understood disease. Eleven ADHR pediatric cases have been described thus far, with cases tending to be more common in females than males. Similar to the general population, two groups of patients with ADHR can be described depending on the mutations present: patients with an R179 and R176 mutation have early-onset of disease and higher frequency of rickets, and a milder and late-onset of disease, respectively. Symptoms and disease severity may fluctuate. Spontaneous remission may occur during the pediatric age.
常染色体显性低磷血症性佝偻病(ADHR)是一种由成纤维细胞生长因子 23 基因突变引起的罕见遗传性佝偻病。ADHR 的特征是由于孤立性肾磷酸盐丢失导致低磷血症。迄今为止,文献中仅报道了少数几例 ADHR 病例。我们描述了一例 17 个月大的女孩,她表现为严重生长不良(身长:-4.08 标准差(SD),体重:-2.2 SD)和低张力。发现低磷血症、肾小管磷酸盐重吸收减少(69%)和佝偻病病变。基因分析显示 FGF23 基因外显子 3 中的杂合变异 c.536G>A(NM_020638.3:c.536G>A),导致 ADHR 的诊断。她接受了磷酸盐盐和口服阿尔法骨化醇治疗。经过 4 年的治疗,在 5 岁时,患者的 ADHR 自发性缓解。鉴于对 ADHR 的认识不足,我们回顾了文献,描述了这种罕见且了解甚少的疾病的特征。迄今为止,已经描述了 11 例儿科 ADHR 病例,女性病例比男性更常见。与一般人群一样,根据存在的突变,可以将 ADHR 患者分为两组:具有 R179 和 R176 突变的患者疾病发病较早,佝偻病的发生率较高,而具有 R206 和 R250 突变的患者疾病发病较晚,分别。症状和疾病严重程度可能会波动。在儿科时期可能会自发缓解。