Menkes病的临床与遗传学特点

Clinical and genetic characteristics of Menkes disease

目的:总结Menkes病(MD)患儿的临床特征与遗传学特点。方法:回顾性病例总结。收集2016年6月至2022年10月郑州大学第三附属医院、郑州大学附属儿童医院和郑州大学第一附属医院儿科确诊的15例MD患儿的临床表现、辅助检查及基因检测结果,并进行随访。结果:15例均为男婴,起病年龄为9 d至5个月15 d,均有皮肤白皙、头发卷曲、全身皮肤松弛、肌张力低下及严重发育迟缓。13例伴癫痫。11例出现贫血,同时有4例伴粒细胞减少。MD患儿血清铜蓝蛋白水平低于同龄健康组婴儿,<3月龄MD患儿铜蓝蛋白水平低于同龄健康组婴儿和>3月龄MD患儿。15例患儿头颅磁共振成像均有异常。12例行头颅磁共振血管造影检查,均表现为颅内血管走行迂曲。15例均有ATP7A基因变异,其中错义变异4例(c.2179G>A 2例),移码变异3例,无义变异3例,外显子缺失3例,剪接位点变异2例。其中1例(c.2968C>T)为未报道的新变异。结论:MD起病年龄早,临床表现多样,但也有特征性的临床表现和辅助检查,确诊靠基因检测,c.2179G>A和外显子缺失可能是我国MD患儿的热点突变。

ObjectiveTo summarize the clinical and genetic characteristics of children with Menkes disease(MD).MethodsThe clinical manifestations,auxiliary examinations and genetic testing results of 15 MD children admitted to the Department of Pediatrics of the Third Affiliated Hospital of Zhengzhou University,Children′s Hospital Affiliated of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from June 2016 to October 2022 were analyzed retrospectively.These children were followed up.ResultsAll the 15 children were male.The age at onset was ranging from 9 days to 5.5 months.White skin,curly hair,skin laxity,hypotonia and severe developmental delay were found in all children,with epilepsy in 13 children,anemia in 11 children and granulocytopenia in 4 children.The concentration of ceruloplasmin in the serum of MD children was lower than that in healthy children of the same age.The concentration of ceruloplasmin in MD children younger than 3 months was significantly lower than that in healthy children of the same age and MD children older than 3 months.The brain magnetic resonance imaging showed abnormalities in all 15 children.Twelve children showed tortuous intracranial vessels in brain magnetic resonance angiography examinations.All the 15 children had ATP7A gene pathogenic variants,including 4 missense variants(2 cases with c.2179G>A),3 frameshift variants,3 nonsense variants,3 exon deletions and 2 splice site variants.Among these children,1 had a novel gene variant that had not been reported so far(c.2968C>T).ConclusionsMD has early onset age and diverse clinical manifestations,but also has characteristic clinical manifestations and applicable auxiliary examinations.Its diagnosis depends on genetic testing.The c.2179G>A and exon deletions may be hot mutations in Chinese MD patients.