Clinical, biochemical，imaging and genetic characteristics of Menkes disease

Abstract:

Objective：To investigate the clinical phenotypes，imaging and genetic features of Menkes disease（MD）. Methods：Seven children were analyzed who were diagnosed as MD by serum ceruloplasmin determination，brain magnetic resonance imaging and gene detection in Children’s Hospital Affiliated to Zhengzhou University from 2016 to 2021. Results：All the 7 cases had the onset to MD at the age of 2 to 6 months，with backward intelligence and movement，sparse and curly hair，white skin，low muscle tone，abnormal hair and face；5 cases were accompanied by convulsions；2 children had feeding difficulties，weakness，fracture and rickets. Serum ceruloplasmin，erythrocyte and hemoglobin decreased and blood lactate increased in 7 children. MRA of the head showed specific tortuous blood vessels and sparse branches. MRI of the head showed subdural effusion，backward development of myelin sheath in white matter，intracranial hemorrhage，abnormal signals in basal ganglia and corpus callosum，brain atrophy，cortical softening and necrosis，hemosiderin deposition，etc. Two children had spontaneous fracture，and one child had obvious rickets-like bone disease. ATP7A gene mutations were detected in 7 children，of which 5 were unreported new mutations. Conclusion：Among the 7 children in this study diagnosed as MD by clinical，biochemical，imaging and genetic examination，5 new mutations of ATP7A gene were found，which guided the family genetic counseling and prenatal diagnosis，and enriched the mutation spectrum of pathogenic genes of MD. A case of MD complicated with fracture was reported for the first time in China.