Reference intervals of plasma catecholamines in newborns for diagnosis of Menkes disease

Menkes disease (#309400) is a rare neurodevelopmental disorder caused by mutations in a copper-transport gene, ATPA7. Clinical symptoms include muscular hypotonia, statomotoric retardation and seizures. Death occurs in most children before three years of age. Treatment with copper histidine may improve long term prognosis if the injections are started within the first days to weeks after birth. Measurement of serum copper and coeruloplasmin shows insufficient sensitivity and specificity in newborns for diagnosis of Menkes disease. Both the measurement of copper in cultured fibroblasts and the molecular analysis of the ATP7A gene could take several weeks for a definitive diagnosis. Another test for diagnosis of Menkes disease is the measurement of plasma catecholamine levels. Because of a defect in the copper-dependent dopamine-β-hydroxylase there are deficiencies in norepinephrine and dihydroxyphenylglycol (DHPG) and excess of dopamine and. dihydroxyphenylacetic acid (DOPAC). Especially the ratio of DOPAC to DHPG was proposed in the literature as a reliable method to diagnose Menkes disease. Reference intervals for the described catecholamine levels for newborns have not been published so far.

We present the catecholamine levels of an 11 month-old caucasian boy with the molecular diagnosis of Menkes disease and reference intervals from 107 term and preterm infants at the age of 1 to 18 weeks of life. The average value for DHPG was 1892 pg/ml, for DOPAC 3218 pg/ml. The ratios of DOPAC to DHPG were 1.72 on average (range: 0.83–3.04).

The stated reference intervals are comparable with data from smaller series in the literature.

Measurement of plasma catecholamines is a promising method for early diagnosis of Menkes diesease in newborns. Following early therapeutic interventions with copper injections can improve outcomes, depending on underlying mutations.