Department of Endocrinology, Genetics and Metabolism, Fuzhou Children's Hospital of Fujian Medical University, No. 145, 817 Middle Road, Fuzhou, 350005, China.
Affiliated Dongfeng General Hospital of Hubei Medical College, Shiyan, 442008, China.
Orphanet J Rare Dis. 2020 Oct 1;15(1):273. doi: 10.1186/s13023-020-01558-7.
Vitamin D-dependent rickets type IA (VDDR-IA) is a rare autosomal recessive disorder characterized by the early onset of severe rickets. The objectives of this study were twofold: (1) to analyze the clinical characteristics and therapy of two patients with VDDR-IA from two separate Chinese families, and (2) investigate the CYP27B1 gene mutations in two large pedigrees.
Medical history, clinical manifestations, physical examination, radiological findings and laboratory data were analyzed from two patients with VDDR-IA. Serum 1, 25-dihydroxyvitamin D [1, 25-(OH)D] of the two patients and their respective families were measured by ELISA and blood samples from both families was obtained for CYP27B1 gene sequence.
Two patients had typical manifestations and radiological evidence of rickets. Laboratory data showed hypocalcaemia and hypophosphataemia, along with high levels of serum alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D However, serum 1,25-(OH)D level were low in the patients but normal in their family members. Genetic sequence identified two patients were homozygous for a duplication mutation in exon 8 of CYP27B1 gene (c.1319_1325dupCCCACCC, p.Phe443Profs * 24). After treating with calcitriol and calcium, there was biochemical improvement with normalization of serum calcium and phosphorus, and radiographic evidence of compensatory skeletal mineralization. One patient developed nephrocalcinosis during follow-up.
This study identified a recurrent seven-nucleotide insertion of CYP27B1 in two large pedigrees, and compared the clinical characteristics and individual therapy of two affected patients. Additionally, our experience further supports the notion that nephrocalcinosis can occur even on standard doses of calcitriol and oral calcium, and normal level of serum calcium, phosphorus, PTH and 25-(OH)D.
维生素 D 依赖性佝偻病 1A 型（VDDR-IA）是一种罕见的常染色体隐性遗传病，其特征为严重佝偻病的早期发病。本研究的目的有两个：（1）分析来自两个中国家庭的 2 例 VDDR-IA 患者的临床特征和治疗方法；（2）研究两个大的家系中 CYP27B1 基因突变。
分析 2 例 VDDR-IA 患者的病史、临床表现、体格检查、影像学发现和实验室数据。采用 ELISA 法检测 2 例患者及其各自家族的血清 1,25-二羟维生素 D [1,25-(OH)2D]，并采集两个家系的血样进行 CYP27B1 基因序列分析。
2 例患者均有典型的佝偻病表现和影像学证据。实验室数据显示低钙血症和低磷血症，伴有血清碱性磷酸酶、甲状旁腺激素和 25-羟维生素 D 水平升高，而患者的血清 1,25-(OH)2D 水平降低，其家族成员的血清 1,25-(OH)2D 水平正常。基因序列分析发现，2 例患者 CYP27B1 基因第 8 外显子均存在纯合性七核苷酸重复插入突变（c.1319_1325dupCCCACCC，p.Phe443Profs*24）。经骨化三醇和钙剂治疗后，生化指标改善，血清钙、磷水平正常，骨骼矿化代偿性增加。1 例患者在随访中出现肾钙质沉着症。
本研究在两个大的家系中发现了 CYP27B1 的重复七核苷酸插入，比较了 2 例患者的临床特征和个体化治疗。此外，我们的经验进一步支持了即使在标准剂量的骨化三醇和口服钙剂治疗下，血清钙、磷、甲状旁腺激素和 25-(OH)2D 水平正常，也可能发生肾钙质沉着症的观点。
