Dopamine beta hydroxylase deficiency

A rare genetic disorder affecting catecholamine synthesis

Dopamine beta hydroxylase deficiency
Synonyms	DβH deficiency, Norepinephrine deficiency
Pronounce
Field	Neurology, Endocrinology, Medical genetics
Symptoms	Orthostatic hypotension, ptosis, nasal congestion, exercise intolerance, hypoglycemia
Complications	Risk of fainting, developmental delay, poor temperature regulation
Onset	Neonatal or early infancy
Duration	Lifelong
Types
Causes	Mutations in the DBH gene leading to absent or inactive dopamine beta-hydroxylase enzyme
Risks	Consanguinity, autosomal recessive inheritance
Diagnosis	Measurement of catecholamine levels (high dopamine, low norepinephrine), genetic testing for DBH mutation
Differential diagnosis	Familial dysautonomia, multiple system atrophy, pure autonomic failure
Prevention	None
Treatment	Supportive care, droxidopa (a synthetic norepinephrine precursor), fludrocortisone, midodrine
Medication	Droxidopa, fludrocortisone, midodrine
Prognosis	Variable; manageable with treatment, but chronic symptoms often persist
Frequency	Extremely rare (less than 100 cases reported worldwide)
Deaths	Rare, usually related to severe hypotension or complications from autonomic dysfunction

Dopamine beta-hydroxylase deficiency is a rare genetic disorder that affects the synthesis of catecholamines, which are important neurotransmitters in the nervous system. This condition is characterized by a deficiency in the enzyme dopamine beta-hydroxylase (DBH), which is responsible for converting dopamine to norepinephrine.

Pathophysiology

Dopamine beta-hydroxylase deficiency results from mutations in the DBH gene, which encodes the enzyme responsible for the conversion of dopamine to norepinephrine. This enzyme is crucial for the production of norepinephrine, a neurotransmitter that plays a key role in the autonomic nervous system and the regulation of blood pressure. Without sufficient DBH activity, individuals have elevated levels of dopamine and reduced levels of norepinephrine and epinephrine.

Clinical Features

The clinical presentation of dopamine beta-hydroxylase deficiency can vary, but common symptoms include:

• Severe orthostatic hypotension, which is a significant drop in blood pressure upon standing, leading to dizziness or fainting.
• Ptosis, or drooping of the eyelids.
• Nasal congestion due to the lack of sympathetic nervous system activity.
• Hypoglycemia, or low blood sugar levels, particularly in infants.
• Exercise intolerance and fatigue.

Diagnosis

Diagnosis of dopamine beta-hydroxylase deficiency is based on clinical symptoms, biochemical tests, and genetic testing. Key diagnostic indicators include:

• Elevated plasma dopamine levels.
• Low or undetectable plasma norepinephrine and epinephrine levels.
• Genetic testing to identify mutations in the DBH gene.

Treatment

Treatment for dopamine beta-hydroxylase deficiency focuses on managing symptoms and may include:

• Droxidopa, a synthetic amino acid that can be converted to norepinephrine, is often used to alleviate symptoms of orthostatic hypotension.
• Fludrocortisone may be prescribed to help increase blood volume and blood pressure.
• Dietary modifications and increased salt intake to help manage blood pressure.

Prognosis

The prognosis for individuals with dopamine beta-hydroxylase deficiency varies depending on the severity of symptoms and the effectiveness of treatment. With appropriate management, many individuals can lead relatively normal lives, although they may need ongoing treatment to manage symptoms.

Related pages

• Catecholamine
• Norepinephrine
• Autonomic nervous system
• Orthostatic hypotension