Prolonged survival in Menkes disease with a novel ATP7A variant: A case report.

BACKGROUND: Menkes disease (MD) is an uncommon, X-linked recessive neurodegenerative disorder caused by mutations in the copper-transporting ATP7A gene, leading to defective copper metabolism. Progressive neurological dysfunction, connective tissue abnormalities, characteristic skeletal and hair findings are defining features of the disease. The prognosis of the classical variant is poor since the majority of patients expire by the age of 3 years. This report presents the first documented case of MD in the Kingdom of Bahrain with a novel ATP7A variant.

CASE SUMMARY: We report a 45-day old male infant presenting with focal seizures and hypotonia. Fair, redundant skin and abnormal hair pigmentation was noted. Neuroimaging revealed classical MD findings like subdural hematoma and arterial tortuosity. In addition, cortical laminar necrosis and craniosynostosis were observed. Diagnostic work-up revealed low serum copper and ceruloplasmin levels with high dopamine levels. Eventually, a novel splice-site mutation in the ATP7A gene was identified using Sanger gene sequencing. A trial of copper-histidine therapy started at the age of 4 months was largely unsuccessful in controlling the disease, with minimal dermatological benefits. Later, the patient developed a large bladder diverticulum at the age of 4 years followed by multiple vascular aneurysms and pseudoaneurysms at 6 years. The patient passed away by the age of 6 years and 9 months most likely due to an aneurysmal rupture.

CONCLUSION: This case illustrates an intermediate phenotype which could be influenced by the new ATP7A variant and demonstrates the phenotypic continuum spectrum in Menkes disease.