Yi Caihong, Xu Juan, He Jiangping, Zhang Xiaofang, Zhang Xianfeng, Huang Jiao
Department of Rheumatology and Immunology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.
Department of Endocrinology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.
Exp Ther Med. 2022 Nov 11;24(6):762. doi: 10.3892/etm.2022.11698. eCollection 2022 Dec.
Vitamin D-dependent rickets (VDDR) type 1A is a rare autosomal recessive disorder caused by cytochrome P450 family 27 subfamily B member 1 (CYP27B1) mutations and can lead to deficiencies in 1α-hydroxylase activity. The present study describes the case of a 39-year-old male patient who presented with rickets and deformities of limbs. Blood biochemical analysis revealed hypocalcemia and high serum parathyroid hormone (PTH) levels. Whole-exome Sanger sequencing using peripheral venous blood of this patient and his parents revealed exon1 c.182T>C, a novel mutation. Through physical examination, laboratory tests, imaging including lower limbs and lumbar spine X-ray and pelvis CT scan, and genetic testing, the patient was diagnosed with VDDR-1A. Following 1 month of treatment with 0.5 µg 1,25-dihydroxy-vitamin D3 twice daily and 0.6 g calcium carbonate once daily, follow-up examinations revealed that the patient's PTH and serum calcium levels had returned to normal. As the patient was diagnosed in his adulthood and missed the optimal treatment period, he developed irreversible deformities. If VDDR-1A can be diagnosed during infancy and childhood, skeletal deformities may be prevented. Therefore, the present report supports the proposal of early genetic sequencing in children with calcium deficiencies for the early diagnosis of rare diseases such as VDDR-1A, -1B and -2A and hereditary hypophosphatemic rickets. Since VDDR-1A diagnosed in adults is rare, the present case may provide clinicians with further insights into the characteristics of this rare disease.
1A型维生素D依赖性佝偻病（VDDR）是一种罕见的常染色体隐性疾病，由细胞色素P450 27家族B成员1（CYP27B1）突变引起，可导致1α-羟化酶活性缺乏。本研究描述了一名39岁男性患者的病例，该患者表现为佝偻病和肢体畸形。血液生化分析显示低钙血症和高血清甲状旁腺激素（PTH）水平。使用该患者及其父母的外周静脉血进行全外显子组Sanger测序，发现外显子1 c.182T>C这一新突变。通过体格检查、实验室检查、包括下肢和腰椎X线及骨盆CT扫描在内的影像学检查以及基因检测，该患者被诊断为VDDR-1A。在每天两次服用0.5μg 1,25-二羟基维生素D3和每天一次服用0.6g碳酸钙治疗1个月后，随访检查显示患者的PTH和血清钙水平已恢复正常。由于该患者在成年期被诊断出来，错过了最佳治疗期，出现了不可逆的畸形。如果在婴儿期和儿童期能够诊断出VDDR-1A，可能会预防骨骼畸形。因此，本报告支持对钙缺乏儿童进行早期基因测序，以早期诊断VDDR-1A、-1B和-2A以及遗传性低磷血症佝偻病等罕见疾病。由于成人中诊断出的VDDR-1A很少见，本病例可能为临床医生进一步了解这种罕见疾病的特征提供参考。
