Dopamine beta-hydroxylase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Dopamine beta-hydroxylase deficiency is a condition that affects the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. The signs and symptoms of dopamine beta-hydroxylase deficiency are caused by a lack of norepinephrine, one of the main chemical messengers (neurotransmitters) of the autonomic nervous system.

Although the signs and symptoms of dopamine beta-hydroxylase deficiency can appear during infancy, people often do not receive a diagnosis until their symptoms worsen during adolescence. Early signs and symptoms may include droopy eyelids (ptosis) and low blood pressure (hypotension). Infants with dopamine beta-hydroxylase deficiency may also experience vomiting, dehydration, decreased body temperature, and low blood glucose (hypoglycemia), which may lead to frequent hospitalizations.

By adolescence or early adulthood, people with dopamine beta-hydroxylase deficiency often have a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. Affected individuals typically experience extreme fatigue during exercise (exercise intolerance) due to their problems maintaining a normal blood pressure.

Other features of dopamine beta-hydroxylase deficiency include nasal congestion, an inability to stand for a prolonged period of time, and retrograde ejaculation, which is a discharge of semen backwards into the bladder.

Symptoms of dopamine beta-hydroxylase deficiency may improve with treatment. If the condition is not treated, symptoms often worsen during adolescence.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the DBH gene cause dopamine beta-hydroxylase deficiency. The DBH gene provides instructions for producing the enzyme dopamine beta-hydroxylase. This enzyme converts dopamine to norepinephrine. Both dopamine and norepinephrine are neurotransmitters that transmit signals from nerve cells to other cells in the body.

The variants in the DBH gene that cause dopamine beta-hydroxylase deficiency prevent the dopamine beta-hydroxylase enzyme from functioning properly. People who lack functional dopamine beta-hydroxylase cannot convert dopamine to norepinephrine. This leads to orthostatic hypotension, exercise intolerance, and the other autonomic nervous system problems seen in people with dopamine beta-hydroxylase deficiency.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Dopamine beta-hydroxylase deficiency is a very rare disorder. As of 2021, approximately 25 individuals with this condition have been described in the scientific literature.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Elevated urinary dopamine · Very frequent (99-80%)

The concentration of dopamine in the urine, normalized for urine concentration, is above the upper limit of normal.

Orthostatic hypotension · Very frequent (99-80%)

A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.

Rhinitis · Very frequent (99-80%)

Inflammation of the nasal mucosa with nasal congestion.

Bilateral ptosis · Very frequent (99-80%)

Anemia · Frequent (79-30%)

A reduction in erythrocytes volume or hemoglobin concentration.

Elevated circulating creatinine concentration · Frequent (79-30%)

An increased amount of creatinine in the blood.

Exercise-induced muscle fatigue · Frequent (79-30%)

An abnormally increased tendency towards muscle fatigue induced by physical exercise.

Fatigue · Frequent (79-30%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Hypoglycemia · Frequent (79-30%)

A decreased concentration of glucose in the blood.

Increased blood urea nitrogen · Frequent (79-30%)

An increased amount of nitrogen in the form of urea in the blood.

Reduced tendon reflexes · Frequent (79-30%)

A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon.

Retrograde ejaculation · Frequent (79-30%)

The emission of semen and seminal fluid into the bladder instead of through the penis during orgasm.

Sleep abnormality · Frequent (79-30%)

An abnormal pattern in the quality, quantity, or characteristics of sleep.

Syncope · Frequent (79-30%)

A transient loss of consciousness (i.e., characterized by a rapid onset, a short duration, and a spontaneous and complete recovery) due to cerebral hypoperfusion.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormal EKG (Occasional (29-5%)); Blurred vision (Occasional (29-5%)); Chest pain (Occasional (29-5%)); Diarrhea (Occasional (29-5%)); Dyspnea (Occasional (29-5%)); Hypothermia (Occasional (29-5%)); Hypotonia (Occasional (29-5%)); Nocturia (Occasional (29-5%)); Orthostatic syncope (Occasional (29-5%)); Vertigo (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Dopamine beta-hydroxylase deficiency is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.