Menkes disease diagnosed by a novel ATP7A frameshift mutation in a patient with infantile spasms-a case report.

Menkes disease (MD) is a rare congenital copper deficiency disease caused by an adenosine triphosphatase copper transporting alpha (ATP7A) gene mutation. It is a progressive and systemic disease that primarily involves the central nervous system and connective tissues. The clinical manifestation of these patients with MD is curly hair, progressive muscle tone reduction, and convulsions, and often leads to death in early infancy. Herein, we present a case of a 9-month-old Chinese male who displayed developmental regression, followed by convulsions, which were characterized by infantile spasms (ISs). The proband also had curly hair, hypopigmented skin, cutis laxa, decreased muscle tone, and micrognathia. The patient's ceruloplasmin levels were below the reference values. Brain magnetic resonance imaging (MRI) showed abnormal signals bilaterally that were symmetrically distributed in the caudate nucleus, globus pallidus, and subcortical white matter of the temporal parietal cortex, white matter in the anterior and posterior corners of the ventricles and the anterior limb of the internal capsule. The electroencephalograph (EEG) showed hypsarrhythmia. Genetic testing revealed a novel frameshift mutation in the ATP7A gene exon 13 and premature termination codon. Copper replacement therapy was initiated after the delayed diagnosis was established. However, the patient still died several months later due to disease progression. Our case reveals a novel frameshift mutation of the ATP7A gene, which expands the gene spectrum of MD. The infants with uncontrollable convulsions, regressive development, curly hair, MD should be considered at early stage and also need the further genetic analysis to confirm MD finally. The correct and timely diagnosis and initiating copper replacement therapy may improve the prognosis.