PMM2-先天性糖基化障碍1例报告并文献复习

PHOSPHOMANNOMUTASE 2-CONGENITAL DISORDER OF GLYCOSYLATION:A CASE REPORT AND LITERATURE REVIEW

目的探讨磷酸甘露糖变位酶2(PMM2)-先天性糖基化障碍(congenital disorders of glycosylation,CDG)患者的临床特点和遗传学特征,为PMM2-CDG患者的早期诊断提供依据。方法对我院收治的1例PMM2-CDG患儿的临床资料进行回顾性分析,并检索中国知网、万方、维普及Pubmed数据库中中国PMM2-CDG患者的临床资料进行分析。结果本例患儿临床表现为生长迟缓、大运动发育落后、皮疹、肌张力低下及肝转氨酶异常,基因组高通量测序分析发现PMM2基因存在一个纯合突变c.634A>G,来自于父母,明确诊断后给予喂养和营养指导、保肝治疗、补充甘露糖等支持疗法并定期复查。患儿6月龄后肝转氨酶恢复正常,1岁后渐呈前额宽大特殊面容,随访至2岁6个月患儿生长迟缓未改善,发育落后逐渐明显。数据库中21例中国PMM2-CDG患者多表现为生长迟缓、发育落后和肌张力低下,颅脑影像学检查可见小脑发育不良,c.395T>C(p.I132T)和c.430T>C(p.P144L)是我国患者出现较多的基因突变类型。结论PMM2-CDG是罕见的先天性代谢性疾病,为常染色体隐性遗传,患者临床出现相关症状时应进行PMM2基因检测以明确诊断。

Objective To investigate the clinical and genetic features of patients with phosphomannomutase 2(PMM2)-congenital disorder of glycosylation(CDG),and to provide a basis for the early diagnosis of PMM2-CDG.Methods A retrospective analysis was performed for the clinical data of a child with PMM2-CDG admitted to our hospital,and CNKI,Wanfang Data,VIP,and PubMed were searched to analyze the clinical data of Chinese patients with PMM2-CDG.Results The child in this study had the clinical manifestations of growth retardation,delayed gross motor development,rash,hypotonia,and abnormal liver aminotransferases.High-throughput genome sequencing revealed a homozygous mutation,c.634A>G,in the PMM 2 gene,which came from the parents.After the diagnosis was clarified,the child was given supportive therapy such as feeding and nutrition gui-dance,liver-protecting treatment,and mannose supplementation and was asked to attend the hospital for regular reexamination.Liver transaminases returned to normal at 6 months of age,and the child gradually developed the unusual facies of wide forehead at 1 year of age.The child was followed up to the age of 2 years and 6 months and showed no improvement in growth retardation,and delayed development gradually became more obvious.Most of the 21 Chinese patients with PMM2-CDG in the above database had the manifestations of growth retardation,delayed development,and hypotonia,with the presence of cerebellar dysplasia on cranial imaging examination,and c.395T>C(p.I132T)and c.430T>C(p.P144L)are common mutations in Chinese patients with PMM2-CDG.Conclusion PMM2-CDG is a rare congenital autosomal recessive metabolic disease,and PMM 2 gene testing should be performed for patients with related symptoms to make a confirmed diagnosis.