Objective: To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants. Method: The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed. Result: Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients. Conclusion: ENPP1 gene mutation was a cause of patient with hypophosphatemic rickets. Comorbid features included generalized arterial calcification of infancy, early onset hearing loss, pseudoxanthoma and ossification of posterior longitudinal ligament. ENPP1 gene testing should be performed on hypophosphatemic rickets patients without PHEX gene variants. Long-term follow up is recommended. The most common types of ENPP1 gene variants were nonsense/splicing variants. The gene c.783C>G was the most common variants in Chinese patients.
目的： 探讨ENPP1基因变异致低磷血症性佝偻病患儿的临床特征和基因变异。 方法： 总结1例2016年8月在首都儿科研究所内分泌科确诊的因ENPP1变异导致的低磷血症性佝偻病患儿临床表现、影像学改变、骨代谢指标及基因等临床资料，并以ENPP1和"低磷血症性佝偻病"及"hypophosphatemic rickets"为关键词，对中国期刊全文数据库、万方数据知识服务平台及美国国家生物技术中心、PubMed 1980年至2017年2月收录的论文进行检索。总结ENPP1基因变异患儿临床表现及基因学特点。 结果： 患儿 女，11岁，因"发现双下肢畸形7年"入院。双膝关节外翻，双下肢X形。血磷0.86 mmol/L,钙2.30 mmol/L,碱性磷酸酶688 U/L。钙磷乘积：25.9。基因检测发现该受检者ENPP1基因在7号外显子发生c.783C>G（p. Tyr 261X）纯合无义变异。受检者父母均携带ENPP1基因c.783C>G（p. Tyr 261X）杂合变异。检索到中文文献1篇（3例），英文文献21篇（17例），共20例患者。均未检出最常见导致低磷血症性佝偻病的PHEX基因变异。发病年龄11月龄~10岁。身材矮小8例，4例失聪，婴幼儿广泛动脉钙化史5例，局部动脉钙化3例，假黄瘤3例，后纵韧带钙化2例。20例共检出ENPP1变异有：9种错义变异，6种剪切变异，4种无义变异。c.783C>G变异见于国内2例患儿。 结论： 低磷血症性佝偻病可由ENPP1基因变异导致，可表现为婴儿广泛动脉钙化、幼年失聪及后纵韧带钙化，故对于PHEX基因阴性的低磷血症性佝偻病可进ENPP1基因检测，需长期随访。ENPP1变异以错义/剪切变异最为常见。国内4例中3例均为c.783C<G。.
Keywords: Hypophosphatemia; Phosphoric diester hydrolases; Rickets.