Identification of a Novel Mutation in the ATP7A Gene in a Korean Patient with Menkes Disease

Menkes disease is an infantile-onset X-linked recessive neurodegenerative disorder caused by diverse mutations in a copper-transport gene, ATP7A. Affected patients are characterized by progressive hypotonia, seizures, failure to thrive and death in early childhood. Here, we report a case of Menkes disease presented by intractable seizures and infantile spasms. A 3-month-old male infant had visited our pediatric clinic for lethargy, floppy muscle tone, poor oral intake and partial seizures. His hair was kinky, brown colored and fragile. Partial seizures became more frequent, generalized and intractable to antiseizure medications. An EEG showed frequent posteriorly dominant generalized spikes that were consistent with a generalized seizure. From a genetic analysis, a c.2743C>T (p.Gln915X) mutation was detected and diagnosed as Menkes disease. The mutation is a novel one that has not been previously reported as a cause of Menkes disease.

A Case of Menkes disease with Infantile Spasm / 대한소아신경학회지

Menkes disease, so called kinky-hair syndrome, is a rare, genetic and progressive neurodegenerative disorder. It is caused by a mutation in the ATP7A gene, which codes for the copper transporting ATPase in the cell organelles. The dysfunction of many copper-dependent enzymes results in low concentration of copper in some tissues and accumulation of copper in others. We report a boy presented with kinky hairs, developmental delay, hypotonia and connective tissue abnormalities at the age of 4 months. Despite the treatment with various antiepileptic drugs, atonic seizures still persisted. At the age of 7 months, his atonic seizures was changed into extensor spasms with modified hypsarrhythmia for some years. The seizure were controlled by topiramate and vigabatrin. At the age of 22 months, serum copper and ceruloplasmin rechecked as 17 ug/dL(80-150 ug/dL) and 7.3 mg/dL(20-46 mg/ dL) respectively. The gene study showed ATP7A mutation and the patient was diagnosed as Menkes disease so that copper-histidine was daily injected. We experienced a case of a 4-month-old boy with Menkes disease and infantile spasm, confirmed by ATP7A mutation.