Identification of a Novel ATP7A Variant in a Chinese Boy With Developmental Delay and Epilepsy

ABSTRACT Menkes disease (MD) is a rare X‐linked recessive syndrome that is caused by mutations in the ATP7A gene, which encodes the P‐type ATP enzyme. The ATP7A gene encodes 1500 amino acids and is expressed in a number of organs, including the brain, muscles, kidneys and lungs. ATP7A transports copper between cell membranes using energy generated by ATP hydrolysis. Patients with the pathogenic variant in the ATP7A gene exhibit a distinctive pattern of severe neurodegeneration, which is often accompanied by specific alterations in hair morphology. The clinical manifestations of MD have been attributed to the dysfunction of copper‐dependent enzymes. Here, we report a 7‐month‐old boy with MD associated with a novel variant of ATP7A (c.1965_1973del, p.Val656_Leu658del). Genetic testing revealed that both his mother and grandmother had identical ATP7A mutations, and we studied this family to better understand the natural history of this syndrome. In this article, we report for the first time the novel mutation in the ATP7A gene in a Chinese family. In our case, he suffers from simian line, developmental delay, epilepsy, hair changes (short, thin, thick, twisted, often light‐coloured), decreased muscle tone, joint relaxation, brain vessel distortion, low serum copper, ceruloplasmin, elevated lactate and an abnormal EEG. Because of its rarity, MD is easily to be misdiagnosed.