Menkes Disease Flashcards
What is the genetic inheritance pattern and mutation associated with a patient who is showing progressive neurocognitive decline and kinky hair seen on physical examination?
Menkes disease
X-linked recessive disorder caused by mutations in the ATP7A gene.
Affects copper transport, therefore the best way to manage this condition is by giving copper.
What are the key clinical features of Menkes disease?
Clinical features include sparse, brittle, and kinky hair, failure to thrive, developmental delays, hypotonia, seizures, and connective tissue abnormalities (e.g., skin laxity, vascular fragility).
There is also an increased risk for developing cerebral aneurysms.
What causes the symptoms of Menkes disease?
Symptoms are due to defective copper transport, leading to copper deficiency in enzymes like lysyl oxidase, cytochrome c oxidase, and dopamine beta-hydroxylase.
The underlying pathophysiology is a collagen cross-linking problem.
What neurological findings are associated with Menkes disease?
Neurological findings include seizures, developmental regression, and neurodegeneration secondary to copper deficiency.
What is the major CNS risk in a patient with Menkes disease?
Increased risk of cerebral aneurysms
How is Menkes disease diagnosed?
Diagnosis is based on clinical presentation, low serum copper and ceruloplasmin levels, and genetic testing for ATP7A mutations.
What is the treatment for Menkes disease?
Treatment involves early administration of copper histidine or copper chloride injections to bypass defective ATP7A transport. Effectiveness depends on early diagnosis.
What systemic complications are seen in Menkes disease?
Complications include vascular rupture due to defective lysyl oxidase, leading to connective tissue fragility, and hypothermia due to impaired mitochondrial function.
What is the prognosis for Menkes disease?
Without treatment, Menkes disease is typically fatal in early childhood due to severe neurological and systemic complications.
What is the role of lysyl oxidase in Menkes disease pathology?
Lysyl oxidase, a copper-dependent enzyme, is involved in collagen cross-linking. Its deficiency leads to connective tissue abnormalities such as skin laxity and vascular fragility.
What distinguishes Menkes disease from Wilson disease?
Menkes disease involves copper deficiency due to defective transport (ATP7A), while Wilson disease involves copper overload due to defective excretion (ATP7B).
