Plasma and CSF levels of catechols in 10 patients with Menkes disease, ranging in age from 9 days to 27 months, were compared with control groups and patients with congenital absence of dopamine-B-hydroxylase (DBH) at the National Institutes of Health, Bethesda, MD. The neurochemical pattern in Menkes disease patients was characterized by high dihydroxyphenylalanine (DOPA), dopamine (DA), and dihydroxyphenylacetic acid (DOPAC) levels, reduced dihydoxyphenylglycol(DHPG) levels, and high ratios of DOPArDHPG and DOPAC:DHPG. In contrast to patients with absent DBH, norepinephrine (NE) levels were normal in 4 Menkes patients and in the CSF of all 10 patients. The pattern was consistent with partial deficiency of DBH activity and compensatory increases in catecholamine biosynthesis in sympathetic nerves and brain. The changes may provide a biochemical marker for Menkes disease. 
COMMENT. Menkes disease (Kinky-Hair disease) is a sex-linked recessive, neurodegenerative disorder of gray matter involving copper metabolism. Clinically, it is characterized by failure to thrive, cherubic facies, twisted and fractured hair, seizures, hypotonia, and progressive psychomotor deterioration. Biochemically, serum copper and cerulo-plasmin levels are reduced or low-normal, and copper uptake by cultured fibroblasts is abnormally increased, permitting intrauterine diagnosis of the disease. Copper levels in liver and brain are low, but are high in the intestine and kidney. The incorporation of copper into enzymes such as DBH requiring this cofactor is impaired. DBH activity was assessed in the present study by measuring levels of DA, NE, and metabolites to provide a picture of catecholamine synthesis and turnover in infants with Menkes disease.