Menkes disease after copper histidine replacement therapy: case report

Area of Science:

• Biochemistry
• Genetics
• Pathology

Background:

• Menkes disease (MD) is a severe X-linked recessive copper metabolism disorder.
• Untreated MD leads to progressive multi-systemic failure, particularly affecting the central nervous system (CNS) and connective tissues, typically resulting in death by age 3.
• Copper-histidine therapy has shown promise in extending survival into adolescence.

Observation:

• This report details the first postmortem pathological examination of an individual with MD treated with copper-histidine, who survived until age 10.
• The examination revealed significant residual pathology in mesenchymal tissues, including skeletal abnormalities, vascular degeneration, and bladder diverticula.
• In contrast, the central nervous system showed minimal pathological changes.

Findings:

• The observed phenotype more closely resembled occipital horn syndrome, a milder allelic disorder, than classic Menkes disease.
• Mesenchymal tissues exhibited more pronounced pathology compared to the CNS following copper-histidine treatment.
• This suggests a differential sensitivity of various tissues to the therapeutic effects of copper-histidine.

Implications:

• The differential response of CNS and mesenchymal tissues may stem from variations in copper-dependent enzyme activity across different cell types.
• Understanding these differential responses is crucial for refining Menkes disease treatment strategies.
• Further research into the molecular mechanisms underlying tissue-specific responses to copper therapy is warranted.