Copper histidine therapy started in a boy at the age of three years – Treatment option for a mild form of Menkes's disease

Aims: Menkes's disease is a rare X-chromosomal-linked disorder of copper metabolism caused by mutations in the ATPA7 gene. Copper deficiency and defective intestinal absorption lead to reduced levels in serum, brain and liver tissue. Main clinical features of Menkes's disease are neurological symptoms in combination with pili torti, metaphyseal changes and alterations of connective tissue. A spectrum of a severe neonatal form to a mild variant and occipital Horn disease are described. A causal therapy does not exist. Therefore a symptomatic multimodal individual therapy is required. Copper histidine therapy has been known since the 1970s. Controversial neurological effects have been reported.

Case report: A three-year-old boy with mental retardation, lethargy and muscular hypotonia is presented. He shows kinky hair, elongation and tortuosity of blood vessels, diverticles of the bladder, hypermobility of joints and ataxia. Diagnosis of Menkes's disease is confirmed by analysis of the ATP7A gene. Family history: healthy, non-consanguineous parents, one healthy sister; one brother died at the age of 10 months by rupture of abnormal abdominal arteries and one intrauterine death of a male fetus. In the course of a multimodal therapy treatment with copper histidine is started at the age of three years at a dose of 1mg per day. After an observation period of 18 months mental and physical abilities are showing progress. Copper histidine therapy is well tolerated. Observed side effects are diarrhoea and an elevation of lithogenic substances in the urine.

Conclusion: Current studies revealed positive effects of copper histidine treatment in patients with Menkes's disease started in the neonatal period, only. Our case report indicates a good response in the case of a toddler and underlines the possibility of late started copper histidine therapy in patients with a milder form of Menkes's disease.