Author(s): Authors Robertson D, Garland EM
Abstract Share this page
Excerpt CLINICAL CHARACTERISTICS: Dopamine beta-hydroxylase (DBH) deficiency is characterized by lack of sympathetic noradrenergic function but normal parasympathetic and sympathetic cholinergic function. Affected individuals exhibit profound deficits in autonomic regulation of cardiovascular function that predispose to orthostatic hypotension. Although DBH deficiency appears to be present from birth, the diagnosis is not generally recognized until late childhood. The combination of ptosis of the eyelids in infants and children, together with hypotension, is suggestive of the disease. In the perinatal period, DBH deficiency has been complicated by vomiting, dehydration, hypotension, hypothermia, and hypoglycemia requiring repeated hospitalization; children have reduced exercise capacity. By early adulthood, individuals have profound orthostatic hypotension, greatly reduced exercise tolerance, ptosis of the eyelids, and nasal stuffiness. Presyncopal symptoms include dizziness, blurred vision, dyspnea, nuchal discomfort, and chest pain. Life expectancy is unknown, but some affected individuals have lived beyond 60 years. DIAGNOSIS/TESTING: The diagnosis of DBH deficiency is based on clinical findings (including poor cardiovascular regulation, other autonomic dysfunction, and intact sweating), physiologic findings of autonomic function (which reveal failure of sympathetic noradrenergic and adrenomedullary function but intact vagal and sympathetic cholinergic function), and unique biochemical features (minimal or absent plasma norepinephrine and epinephrine AND a five- to tenfold elevation of plasma dopamine, a finding probably pathognomonic of DBH deficiency). DBH deficiency is caused by biallelic pathogenic variants in DBH. MANAGEMENT: Treatment of manifestations: Administration of L-threo-3,4-dihydroxyphenylserine (droxidopa) alleviates the orthostatic hypotension and other symptoms. Affected individuals do not respond as well to standard therapeutic approaches for autonomic failure. Surgery can correct ptosis. Prevention of primary manifestations: Droxidopa can improve the orthostatic hypotension and symptoms, but these recur if treatment is stopped. Surveillance: Renal function (measurement of plasma creatinine and BUN concentrations) is assessed every two years or more often if loss of renal function is evident. Plasma magnesium and potassium should also be assessed. Agents/circumstances to avoid: Untreated individuals should avoid hot environments, strenuous exercise, standing motionless, and dehydration. Pregnancy management: Routine blood pressure monitoring during pregnancy and delivery, with adjustment of droxidopa dosage as needed; extra doses of droxidopa may be required during delivery and dose adjustment may be required post partum. GENETIC COUNSELING: DBH deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25\% chance of being affected, a 50\% chance of being an asymptomatic carrier, and a 25\% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives is possible if both pathogenic variants in the family are known. If the pathogenic variants have been identified in an affected family member, prenatal testing for at-risk pregnancies is possible through laboratories offering either prenatal testing for the gene of interest or custom testing. Copyright © 1993-2016, University of Washington, Seattle. All rights reserved.
This article was published in Dopamine Beta-Hydroxylase Deficiency
and referenced in Journal of Genetic Syndromes & Gene Therapy