Summary
Menkes disease is a copper metabolism disorder. Its incidence is estimated at 1/250 000 births. Clinical signs include ante- and postnatal growth retardation and progressive neurological deterioration manifesting within the first two months of life as axial hypotonia, spasticity, hypothermia, feeding difficulties, and partial or generalized convulsions. Psychomotor regression and microcephaly develop later. Hair and eyebrows have a remarkable phenotype: they are sparse, brittle, dull, hypopigmented and twisted. Microscope examination reveals pili torti and monilethrix (periodic narrowing). The skin is dry and thick. The face is chubby. Ligamentous hyperlaxity, skin hyperelasticity, bladder and uretera diverticula can occur. Aneurysms develop in long, tortuous vessels with irregular lumens, giving rise to sub-dural, intracerebral or intestinal haemorrhages. Radiologically, bone abnormalities appear as pseudorachitism. The disease is associated with mutations in the ATP7A gene, localised to Xq13.3 and encoding an intracellular copper transport protein. Menkes and "occipital horn syndrome'' are allelic (see this disease). The symptoms result from a defect in the function of copper-dependent enzymes. Diagnosis can be established by detecting low levels of copper (and caeruloplasmin) in the serum, and high levels in cutaneous fibroblasts. The diagnosis can be confirmed by identification of the gene mutation. Genetic analysis also allows screening of carrier females (who may have patches with cutaneous and hair anomalies) and antenatal diagnosis through chorionic villus sampling. Treatment based on parenteral administration of histidine-copper delays the onset of neurological signs and increases lifespan. Prognosis is poor, with death often occurring in the first three years of life. *Author: Dr M-P. Cordier-Alex (June 2006)*.
