Dopamine beta-hydroxylase deficiency.
Dopamine beta-hydroxylase (DbetaH) deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DbetaH deficiency is unknown. Only a limited number of cases with this disease have been reported. DbetaH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DbetaH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS). Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.
Senard
Jean-Michel
JM
Club d'Etude du Système Nerveux Autonome, Autonomic Unit of the Department of Clinical Pharmacology and INSERM U586, Faculté de Médecine, 37 allées Jules Guesde, 31073 Toulouse cedex, France. senard@cict.fr
Rouet
Philippe
P
D001341:Autonomic Nervous System / Q000201:enzymology; D003677:Deficiency Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D003937:Diagnosis, Differential; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000209:etiology / Q000628:therapy; D009154:Mutation; D011379:Prognosis
D004299:Dopamine beta-Hydroxylase