[From gene to disease; dopamine-beta-hydroxylase deficiency and orthostatic hypotension].
The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that catalyses the formation of norepinephrine from dopamine. Inactivation of this enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic failure of the sympathetic nervous system. This manifests as a severe orthostatic syndrome in which sweating and a normal parasympathetic function are preserved. Several mutations of the DBH gene that cause this very rare syndrome have now been identified. Diagnosis is made on the basis of clinical features and the finding of increased plasma dopamine in the near-absence of norepinephrine. A sole finding of absent plasma DbetaH is insufficient, since about 4% of the population have absent DbetaH. This trait cosegregates with a polymorphism in the promoter region of the DBH gene and is not associated with sympathetic failure. The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by the ubiquitous aromatic-L-amino acid decarboxylase.
Deinum
J
J
Afd. Algemeen Inwendige Geneeskunde, Universitair Medisch Centrum St Radboud, Geert Grooteplein 8, 6525 GA Nijmegen. j.deinum@aig.umcn.nl
van den Meiracker
A H
AH
Boomsma
F
F
van Ittersum
F J
FJ
Wevers
R A
RA
Lenders
J W M
JW
D004298:Dopamine / Q000096:biosynthesis / Q000097:blood; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000235:genetics*; D009154:Mutation; D009638:Norepinephrine / Q000096:biosynthesis / Q000097:blood; D013546:Sweating / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology
D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine