Infants diagnosed with Menkes disease early by plasma neurochemical methods and treated early, within 22 days after birth, with copper replacement therapy, had a 92% survival rate vs 13% in those treated late, Median follow-up in 12 newborns treated early was 4.6 years compared to 1.8 years in 15 diagnosed and treated late. Abnormally low copper dependent, dopamine-B-hydroxylase activity was identified by measuring plasma catecholamine levels in infants at risk. Response to treatment occurred only in patients with ATP7A mutations that permit some residual copper transport. [1]

COMMENT. Menkes disease is an X-linked recessive infantile neurodegenerative disease caused by deficiency of a copper-transporting ATPase, ATP7A. Enzymes that require copper as a cofactor (dopamine-B-hydroxylase, cytochrome coxidase) are decreased. Symptoms are delayed for 6 to 8 weeks after birth. The disease is characterized by hypotonia, seizures, failure to thrive, and death by 3 years of age. Biochemical markers such as low serum copper and ceruloplasmin are unreliable in the neonatal period since they are low in normal neonates and overlap with the values found in Menkes disease. A molecular diagnosis, involving measurement of dopamine, norepinephrine and other catecholamines in plasma, is necessary to identify cases before symptoms develop and for copper replacement therapy to be successful.