Makindo Medical Notes

Menkes disease is an X-linked recessive disorder that affects connective tissue due to impaired copper absorption and transport. It results from mutations in the ATP7A gene, which is responsible for copper transport. This contrasts with Wilson disease, where a defect in the ATP7B gene leads to copper buildup in tissues.

Pathophysiology:

Copper is a crucial cofactor for various enzymes, including lysyl oxidase, which is responsible for collagen cross-linking. In Menkes disease, defective ATP7A leads to copper deficiency, reducing lysyl oxidase activity and resulting in defective collagen cross-linking. This impaired collagen cross-linking weakens connective tissues.

Clinical Features:

• Brittle, "kinky" hair: Characteristic abnormal hair due to defects in hair keratin cross-linking.
• Growth and developmental delays: Children with Menkes disease often experience growth failure and developmental delays.
• Hypotonia: Muscle weakness and reduced muscle tone are common in affected individuals.
• Increased risk of cerebral aneurysms: Weak connective tissue in blood vessels increases the risk of aneurysms and hemorrhagic strokes.

Diagnosis:

• Clinical presentation: Diagnosis is often suspected based on characteristic features such as brittle hair, developmental delays, and hypotonia.
• Laboratory testing: Low serum copper and ceruloplasmin levels confirm copper deficiency.
• Genetic testing: Molecular analysis of the ATP7A gene confirms the diagnosis by identifying mutations.
• Skin biopsy: May show abnormalities in collagen cross-linking and can aid in diagnosis.

Management:

• Copper supplementation: Early treatment with subcutaneous or intravenous copper injections (e.g., copper histidine) may improve outcomes if started before significant neurological damage occurs.
• Supportive care: Includes physical and occupational therapy to manage developmental delays and improve muscle strength.
• Monitoring for complications: Regular assessments for potential complications such as cerebral aneurysms and seizures are critical for management.
• Unfortunately, prognosis is poor if treatment is delayed, as neurological damage becomes irreversible.

Comparison with Wilson Disease:

• Menkes disease: Involves copper deficiency due to impaired copper transport (mutation in ATP7A).
• Wilson disease: Involves copper buildup due to defective copper excretion (mutation in ATP7B).