Dopamine beta-hydroxylase deficiency is a rare genetic condition that impacts the body’s ability to produce neurotransmitters. This disorder affects the autonomic nervous system, which regulates involuntary bodily processes like blood pressure and body temperature. While symptoms can appear in infancy, diagnosis often occurs later in adolescence or adulthood as symptoms become more pronounced.
Understanding the Deficiency
Dopamine beta-hydroxylase (DBH) is an enzyme that converts dopamine into norepinephrine. This conversion is a step in synthesizing catecholamines, including norepinephrine and epinephrine (adrenaline). A deficiency in DBH disrupts this pathway, leading to very low or undetectable levels of norepinephrine and epinephrine. Simultaneously, dopamine levels become significantly elevated, often five to tenfold higher than normal.
This deficiency is caused by mutations in the DBH gene. These mutations prevent the enzyme from functioning correctly or being produced, resulting in the characteristic imbalance of neurotransmitters. The condition is inherited in an autosomal recessive manner, requiring two mutated gene copies, one from each parent, to develop the disorder.
Identifying the Symptoms
The lack of norepinephrine and epinephrine significantly affects the autonomic nervous system, leading to various symptoms. Orthostatic hypotension, a sharp drop in blood pressure upon standing, is common, causing dizziness, blurred vision, or fainting. This symptom often becomes more severe in adolescence or early adulthood.
Individuals with DBH deficiency frequently experience exercise intolerance, extreme fatigue during physical activity due to difficulty maintaining stable blood pressure. Other signs of autonomic dysfunction include droopy eyelids (ptosis) and persistent nasal congestion. Some males may also experience retrograde ejaculation.
In infants, early symptoms can be severe, including vomiting, dehydration, hypothermia, and hypoglycemia, often leading to frequent hospitalizations. Developmental delays, particularly in motor skills, can occur, though the condition generally has a minor impact on cognitive function. Less common features may include abnormal kidney function, joint laxity, or anemia.
Diagnosis and Treatment Approaches
Diagnosing dopamine beta-hydroxylase deficiency involves clinical evaluation and laboratory tests. A key indicator is measuring catecholamine levels in the blood. Individuals with DBH deficiency show minimal or absent norepinephrine and epinephrine, while dopamine levels are significantly elevated. These markers help differentiate DBH deficiency from other autonomic disorders.
Genetic testing confirms the diagnosis by identifying mutations in the DBH gene. While plasma DBH enzyme activity can be tested, it may not be conclusive due to common genetic variations that can falsely indicate an absence of activity.
The primary treatment involves droxidopa (L-threo-dihydroxyphenylserine), a synthetic precursor to norepinephrine. It is converted into norepinephrine by dopa decarboxylase, bypassing the deficient DBH enzyme. This increases norepinephrine levels, helping to restore blood pressure and alleviate symptoms like orthostatic hypotension and exercise intolerance. Typical oral doses range from 100 to 500 mg, taken two or three times daily. Supportive care focuses on avoiding triggers that worsen symptoms: hot environments, strenuous exercise, prolonged standing, and dehydration.