Dopamine β-Hydroxylase Deficiency Associated with Mutations in a Copper Transporter Gene

Abstract

Publisher Summary This chapter focuses on what is arguably the most important aspect of the trial, characterization of a distinctive neurochemical pattern that has proven extremely useful as a rapid and reliable diagnostic marker for Menkes disease and OHS. Over the past 6 years, the National Institutes of Health has offered a treatment protocol (parenteral copper replacement) for infants and children with these disorders. This abnormal neurochemical pattern includes the plasma and/or cerebrospinal fluid (CSF) concentrations of five catechols (dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, norepinephrine, and dihydroxyphenylglycol) whose levels are directly influenced by the activity of dopamine β-hydroxylase (DBH), a copper-containing enzyme. Quantitation of plasma and/or CSF catechol levels provides a sensitive and specific indicator of partial DBH deficiency in humans with mutations in ATP7A. The assay has a particularly valuable application in the very early identification of affected infants, for whom diagnosis by clinical or alternative biochemical parameters is problematic, and who may benefit significantly from early recognition and treatment. As ob served, Menkes disease patients show a neurochemical pattern that is similar to that in patients with congenital absence of DBH: elevated levels of dihydroxyphenylalanine, dihydroxyphenylacetic acid, and dopamine and low levels of dihydroxyphenylglycol.