表现为类佝偻病的遗传性疾病

Rickets-like genetic diseases

总结在发育儿科或儿童保健门诊因腿弯、前囟未闭、头发少等类佝偻病症状就诊的遗传性疾病的临床特点、致病基因及治疗进展,这些遗传性疾病包括低血磷抗维生素D佝偻病、低碱性磷酸酶血症、软骨发育不全、维生素D依赖性佝偻病、致密性骨发育不全和外胚层发育不全。低血磷抗维生素D佝偻病的患儿经常以腿弯、生长迟缓就诊,生化检查血磷明显降低,临床容易诊断。该病治疗与营养性维生素D缺乏性佝偻病不同,需要用1,25羟维生素D3和磷酸盐合剂治疗。低碱性磷酸酶血症特点为碱性磷酸酶明显降低,血钙和磷正常,是由于TNSALP基因突变所致。软骨发育不全患儿除腿弯外,还存在短肢型矮小和特殊面容,血钙、磷和碱性磷酸酶等生化检查均正常,骨骼X线及FGFR3基因检测有助于诊断。维生素D依赖性佝偻病为常染色体隐性遗传,治疗中可选择补充生物活性的维生素D。致密性骨发育不全患儿可因前囟大就诊,此类患儿除了前囟大以外,还伴有下颌角消失、牙齿及指甲发育差等表现,系TSK基因突变所致。外胚层发育不全患儿可因头发少就诊,易误诊为营养性维生素D缺乏性佝偻病,与EDA、EDAR、EDARADD及WNT 10A 4种基因有关。

This paper summarizes the clinical features, causative genes and treatment progress of patients with rickets-like genetic diseases, including X-linked hypophosphatemic rickets （XLH）, hypophosphatasia, achondroplasia, vitamin D-dependent rickets, pycnodysostosis and ectodermal dysplasia, who visited the pediatric or child health clinic due to the symptoms of rickets, including bow legs, delayed closure of the anterior fontanelle, and sparse hair. Children with XLH usually go to hospital for bow legs and short stature, and biochemical evaluation reveals significantly low serum phosphorus so it is easily diagnosed. This disease is treated using phosphate mixture and 1,25（OH）2D3, which is different from the treatment of nutritional vitamin D deficiency rickets. Hypophosphatasia is characterized by a significant decrease in serum alkaline phosphatase, as well as normal serum calcium and phosphorus. The disease is caused by mutations in TNSALP gene. Patients with achondroplasia show short-limbed dwarfism and special face in addition to bow legs, but with normal serum calcium, phosphorus and alkaline phosphatase. Bone X-ray and FGFR3 gene test contribute to the diagnosis. Vitamin D-dependent rickets is an autosomal recessive disease, and active vitamin D supplement is effective in treatment of the disease. Patients with pycnodysostosis may be first seen at hospital because of large anterior fontanelle; in addition, they also show obtuse mandibular angle, dental abnormalities and dysplastic nails, which are caused by mutations in TSK gene. Children with ectodermal dysplasia may see a doctor for sparse hair, and they are easily misdiagnosed with nutritional vitamin D deficiency rickets. Ectodermal dysplasia is related to EDA, EDAR, EDARADD and WNT 10A genes.