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Dopamine beta-hydroxylase deficiency
This condition primarily affects the autonomic nervous system, leading to symptoms such as low blood pressure, difficulty regulating body temperature, and muscle weakness. It typically appears in infancy or early childhood.
Overview
Dopamine beta-hydroxylase (DBH) deficiency is a very rare inherited disorder impacting the autonomic nervous system. This system controls essential bodily functions, including heart rate, blood pressure, digestion, and body temperature, without conscious effort [PMID:36528761]. In DBH deficiency, the body cannot produce noradrenaline (also called norepinephrine) and adrenaline (epinephrine), two important neurotransmitters. These chemicals are crucial for regulating stress responses and maintaining normal body functions. The absence of these neurotransmitters leads to a range of symptoms, predominantly affecting blood pressure and temperature control.
Symptoms & clinical features
Individuals with DBH deficiency often experience severe low blood pressure when standing up (orthostatic hypotension), which can cause dizziness, fainting, and collapses [PMID:36528761]. Other common features include a reduced ability to regulate body temperature, leading to difficulties coping with heat or cold. Muscle weakness and low muscle tone (hypotonia) can also be present, particularly in infancy, which may affect motor development. Some individuals may have nasal congestion, drooping eyelids (ptosis), and difficulties with ejaculation in males [PMID:36528761]. Symptoms typically begin in infancy or early childhood, though the severity and specific presentation can vary greatly between individuals.
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Affected organs
The primary organs and systems affected by DBH deficiency are those controlled by the autonomic nervous system. This includes the cardiovascular system, leading to issues with blood pressure regulation. The thermoregulatory system, responsible for maintaining body temperature, is also significantly impacted. The smooth muscles in various organs, such as those involved in digestion and urinary function, can be affected. Additionally, the adrenal glands, which typically produce adrenaline, are unable to do so effectively in this condition.
Risks & severity
The severity of DBH deficiency can vary, but it often presents with significant challenges, especially related to blood pressure control. The chronic low blood pressure can lead to recurrent fainting spells and a risk of injury from falls. The inability to regulate body temperature can also pose risks in extreme environmental conditions. While the exact prevalence is not well established due to its rarity, understanding the condition early is important for managing symptoms and improving quality of life. Without appropriate treatment, the symptoms can severely impact daily activities and general well-being. The condition is usually identified in infancy or early childhood.
Genetic causes
Dopamine beta-hydroxylase deficiency is caused by pathogenic variants in the DBH gene. The DBH gene provides instructions for making an enzyme called dopamine beta-hydroxylase. This enzyme plays a vital role in the nervous system, specifically in the process of creating neurotransmitters [PMID:24075191]. Its function is to convert dopamine into noradrenaline. Noradrenaline is essential for regulating functions such as blood pressure and heart rate, and it is further converted into adrenaline. When pathogenic variants occur in the DBH gene, the enzyme either does not function correctly or is not produced at all. This disruption means that dopamine cannot be converted into noradrenaline and adrenaline, leading to the accumulation of dopamine and the absence of the other two crucial neurotransmitters throughout the body.
- DBH dopamine beta-hydroxylase
Inheritance pattern
Dopamine beta-hydroxylase deficiency typically follows an autosomal recessive inheritance pattern. This means that an individual must inherit two altered copies of the DBH gene, one from each parent, to develop the condition [PMID:24075191]. People who have only one altered copy of the DBH gene are carriers; they usually do not show symptoms of the condition themselves. If two carriers have children, there is a 25% chance with each pregnancy that their child will inherit two altered copies of the gene and develop the condition, a 50% chance the child will be a carrier, and a 25% chance the child will inherit two unaffected copies and not be a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosing DBH deficiency often begins with recognising characteristic clinical symptoms such as severe orthostatic hypotension and difficulty with temperature regulation. Blood tests showing very low or undetectable levels of noradrenaline and adrenaline, along with elevated levels of dopamine, can strongly suggest the diagnosis [PMID:36528761]. Confirmation of the diagnosis is typically achieved through genetic testing, which identifies pathogenic variants in the DBH gene. In the UK, individuals suspected of having this condition would usually be referred to Clinical Genetics services by their GP or a specialist. Genetic testing for DBH deficiency is available through the NHS Genomic Medicine Service, often guided by specific R-codes related to inherited metabolic disorders, such as R344 Primary orthostatic intolerance.
Management & lifestyle
Management for DBH deficiency focuses on replacing the missing neurotransmitter noradrenaline. The most common treatment involves administering a medication called L-threo-dihydroxyphenylserine (L-DOPS), which the body can convert directly into noradrenaline [PMID:24075191]. This helps to alleviate many symptoms, particularly improving blood pressure control. Other supportive measures may include increasing salt and fluid intake, wearing compression stockings, and avoiding triggers such as prolonged standing or hot environments. Regular monitoring by a specialist team, including a neurologist and paediatrician or endocrinologist where appropriate, is part of the ongoing care. These specialists can help adjust treatment as needed and manage any emerging symptoms within the NHS framework.
UK care pathway
In the UK, if DBH deficiency is suspected, initial assessment may be performed by a GP or a specialist. Referral to Clinical Genetics is a key step, facilitated by the NHS Genomic Medicine Service. Genetic counsellors play an important role, providing information about the condition, inheritance patterns, and support for families. Diagnosis involves genetic testing, which is available through the NHS and often aligns with specific R-codes on the National Genomic Test Directory. Multidisciplinary teams, including neurologists and endocrinologists, typically provide ongoing care and management.
Frequently asked questions
What is the main problem in Dopamine beta-hydroxylase deficiency?
The main problem is that the body cannot produce enough noradrenaline and adrenaline due to a faulty enzyme. This leads to issues with controlling blood pressure, heart rate, and body temperature.
How is this condition inherited?
It is inherited in an autosomal recessive pattern. This means a child must inherit a faulty gene copy from both parents to develop the condition. Parents who each carry one faulty copy typically do not have symptoms themselves.
Can Dopamine beta-hydroxylase deficiency be treated?
Yes, it can be treated by replacing the missing noradrenaline. A medication called L-DOPS is commonly used, which the body converts into noradrenaline, helping to manage symptoms like low blood pressure.
What kind of doctor treats this condition in the UK?
In the UK, care for DBH deficiency is often provided by a team of specialists, including neurologists, paediatricians, endocrinologists, and clinical geneticists, within the NHS.
Is this a common condition?
No, Dopamine beta-hydroxylase deficiency is considered a very rare condition. Its exact prevalence is not well established.
References
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- Senard JM, Rouet P. Dopamine beta-hydroxylase deficiency. Orphanet journal of rare diseases. 2006. PMID: 16722595
- Timmers HJ, Deinum J, Wevers RA. Congenital dopamine-beta-hydroxylase deficiency in humans. Annals of the New York Academy of Sciences. 2004. PMID: 15240410
- Wassenberg T, Deinum J, van Ittersum FJ. Clinical presentation and long-term follow-up of dopamine beta hydroxylase deficiency. Journal of inherited metabolic disease. 2021. PMID: 33034372
- Biaggioni I, Goldstein DS, Atkinson T. Dopamine-beta-hydroxylase deficiency in humans. Neurology. 1990. PMID: 2300263
- Arnold AC, Garland EM, Celedonio JE. Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency. The Journal of clinical endocrinology and metabolism. 2017. PMID: 27778639
- Biaggioni I, Hollister AS, Robertson D. Dopamine in dopamine-beta-hydroxylase deficiency. The New England journal of medicine. 1987. PMID: 3683474
- Robertson D, Haile V, Perry SE. Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension (Dallas, Tex. : 1979). 1991. PMID: 1677640