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.
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 indicate that complete DBH deficiency encompasses sympathetic noradrenergic failure and adrenomedullary failure but intact vagal and sympathetic cholinergic function. Biochemical features unique to DBH deficiency include minimal or absent plasma norepinephrine and epinephrine AND a five- to tenfold elevation of plasma dopamine, a finding probably pathognomonic of DBH deficiency. Molecular genetic testing of DBH, the only gene in which mutations are known to cause DBH deficiency is available on a clinical basis.
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 disease-causing mutations in the family are known. No laboratories offering molecular genetic testing for prenatal diagnosis of dopamine beta-hydroxylase deficiency are listed in the GeneTeststrade mark Laboratory Directory; however, prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutations have been identified.