Autonomic Disorders Consortium

Information for Professionals

Disorders In Depth

Dopamine-Beta-Hydroxylase Deficiency (DBH)

Introduction

Norepinephrine and epinephrine are crucial determinants of minute-to-minute neural regulation of blood pressure and are also present at central nervous system sites likely to be involved in a variety of behaviors. Norepinephrine and epinephrine thus seem so important to human beings that it seemed unlikely for many years that subjects without these catecholamines would survive the perinatal period and develop to adulthood.
This view changed with recognition of a congenital syndrome of severe orthostatic hypotension, noradrenergic failure, and ptosis of the eyelids in two young adults. The syndrome differs from familial dysautonomia and various autonomic disorders seen in adults in that the defect can be localized to the noradrenergic and adrenergic tissues. There is virtual absence of norepinephrine, epinephrine, and their metabolites. However, there is greatly increased dopamine in plasma, cerebrospinal fluid, and urine.

Symptoms

Physical Examination

Testing

Genetics

The DBH gene is located at 9q34. In 2000, the genomic basis of DBH deficiency was elucidated. Kim et al. identified seven novel variants, including four potentially pathogenic mutations, in the human DBH gene of two unrelated DBH deficient patients and their families. Both patients had an intronic mutation that can lead to aberrant splicing. However, this mutation generates both aberrant and properly spliced DBH messages, and patients with DBH deficiency have no DBH gene product, even when a polyclonal antibody against DBH is used to measure it. It is possible that another variant at DBH is necessary to produce the DBH deficiency phenotype.

Treatment

Prospectus

DBH deficiency and its successful treatment by DOPS has provided valuable lessons in catecholamine pharmacology and encourages us to hope that other autonomic disorders may one day also yield to genuinely effective therapeutic intervention. Indeed, other newly recognized genetic autonomic and catecholamine disorders are now being recognized, including tetrahydrobiopterin deficiency, dopa decarboxylase deficiency. Menkes disease, monoamine oxidase deficiency and other disorders of dopamine metabolism.