dopamine beta-hydroxylase deficiency

Dopamine beta-hydroxylase (DBH) deficiency is a rare genetic disorder that affects the autonomic nervous system, which controls involuntary body processes such as heart rate, blood pressure, and digestion.

Characteristics of DBH Deficiency

• Severe early onset orthostatic hypotension [3] - This means that individuals with DBH deficiency experience a significant drop in blood pressure when standing up from a sitting or lying down position.
• Hypothermia and hypoglycemia can occur in the neonatal period [3] - This refers to low body temperature and low blood sugar levels at birth.

Causes of DBH Deficiency

• The disorder is caused by a genetic change in the DBH gene, which provides instructions for producing the dopamine beta-hydroxylase enzyme [4][7].
• The DBH gene is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition [4].

Enzyme Responsible

• Dopamine beta hydroxylase is the enzyme responsible for converting dopamine to norepinephrine [6].
• The absence or malfunctioning of this enzyme leads to a complete inability to synthesize norepinephrine, epinephrine, and other related hormones [8].

Treatment Options

• Fludrocortisone at relatively high doses has been used to raise blood pressure with some benefit [2].
• Indomethacin has also shown modest benefits in raising blood pressure [2].

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Signs and Symptoms of Dopamine Beta-Hydroxylase Deficiency

Dopamine beta-hydroxylase (DBH) deficiency is a rare genetic disorder that affects the autonomic nervous system, which controls involuntary body processes such as blood pressure regulation and body temperature. The signs and symptoms of DBH deficiency can vary in severity and may not appear until late childhood or adolescence.

Common Signs and Symptoms:

• Profound Orthostatic Hypotension: A significant drop in blood pressure when standing up from a sitting or lying down position, which can lead to dizziness, fainting, or even loss of consciousness.
• Ptosis (Droopy Eyelids): Drooping eyelids due to weakness in the muscles that control eye movement.
• Reduced Exercise Tolerance: A decrease in physical endurance and ability to engage in strenuous activities.
• Nasal Congestion: Stuffy or runny nose, which can be persistent and resistant to treatment.
• Sleep Difficulties: Problems with falling asleep or staying asleep throughout the night.

Other Possible Symptoms:

• Vomiting
• Dehydration
• Low blood sugar levels (hypoglycemia)
• Dizziness
• Blurred vision
• Severe neuropathic or limb pain
• Telangiectasias and angiokeratomas (abnormal blood vessel formations on the skin)

Important Note:

The symptoms of DBH deficiency can be similar to those of other conditions, making diagnosis challenging. A comprehensive medical evaluation, including genetic testing, is essential for accurate diagnosis and treatment.

References:

[1] - Profoundly decreased blood pressure (Hypotension) [2] [3] - Ptosis of the eyelids, reduced exercise tolerance, a ... [2] [4] - 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. [10] [5] - Symptoms include vomiting, dehydration, low blood pressure, especially upon standing (orthostatic hypotension), and low blood sugar levels (hypoglycemia). [12] [6] - Dopamine beta-hydroxylase deficiency is a disease which affects the body's ability to regulate blood pressure and body temperature. Symptoms typically begin in late childhood and include vomiting, dehydration, low blood pressure, especially upon standing (orthostatic hypotension), and low blood sugar levels (hypoglycemia). [12] [7] - This enzyme, known as dopamine beta-hydroxylase (DBH), plays a crucial role in the synthesis of important neurotransmitters in your body. When this enzyme is deficient or absent, it can lead to a rare but significant condition called dopamine beta-hydroxylase deficiency. [13] [8] - 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. [15]

Diagnostic Tests for Dopamine Beta-Hydroxylase Deficiency

Dopamine beta-hydroxylase (DBH) deficiency is a rare genetic disorder that affects the production of certain neurotransmitters. Diagnosing this condition requires a combination of clinical evaluation, biochemical tests, and molecular genetic testing.

• Biochemical Tests: These tests measure the levels of various neurotransmitters in the blood or urine. Specifically, DBH deficiency is characterized by:
  • Minimal or absent plasma concentrations of norepinephrine and epinephrine [5]
  • A five- to ten-fold elevation of plasma dopamine [5]
• Molecular Genetic Testing: This test involves analyzing the DNA sequence of the DBH gene to identify any mutations that may be causing the deficiency. The diagnosis is confirmed by demonstrating biallelic pathogenic variants in DBH [14].
• Other Tests: In some cases, additional tests such as muscle sympathetic nerve activity measured by microneurography or spectral analysis of beat-to-beat values of R–R interval and blood pressure may be performed to support the diagnosis [11].

Interpretation of Test Results

The interpretation of test results should be done in consultation with a geneticist, neurologist, and other specialists as needed. The diagnostic teams for DBH deficiency may include genetics, neurology, ophthalmology, and others [10]. A primary care physician (PCP) can help coordinate referrals and testing [10].

References

[5] - Minimal or absent plasma concentrations of norepinephrine and epinephrine are characteristic of DBH deficiency. [14] - Molecular genetic testing confirms the diagnosis by demonstrating biallelic pathogenic variants in DBH. [11] - Additional tests such as muscle sympathetic nerve activity measured by microneurography may be performed to support the diagnosis.

Dopamine beta-hydroxylase (DBH) deficiency is a rare genetic disorder that affects the production of norepinephrine, a crucial neurotransmitter involved in various bodily functions such as blood pressure regulation and heart rate control. The condition is characterized by severe orthostatic hypotension, which can lead to dizziness, fainting, and other complications.

Fortunately, there are effective treatment options available for DBH deficiency. One of the most promising treatments is Droxidopa (Northera), a synthetic norepinephrine precursor that has been shown to replenish norepinephrine levels in the body [6][8]. Studies have demonstrated that Droxidopa can increase blood pressure, improve symptoms of hypotension, and enhance orthostatic tolerance in patients with DBH deficiency [7].

Another treatment option is Fludrocortisone, a medication that provides some benefit in managing orthostatic hypotension associated with DBH deficiency. However, it's essential to note that marked orthostatic hypotension still persists despite treatment with Fludrocortisone [9].

It's worth mentioning that Droxidopa has been found to have additional benefits beyond just treating DBH deficiency. Research has shown that it can also improve glucose homeostasis and insulin sensitivity in patients, making it a valuable therapeutic option for managing related metabolic complications [7].

In summary, the drug treatment of dopamine beta-hydroxylase deficiency primarily involves the use of Droxidopa (Northera) to replenish norepinephrine levels and alleviate symptoms. Fludrocortisone may also be used as a supplementary treatment to manage orthostatic hypotension.

References: [6] - February 9, 2024 - Studies have explored the connection between DβH deficiency, Droxidopa treatment, and the effect on orthostatic tolerance and glucose homeostasis. [7] - February 9, 2024 - Studies have explored the connection between DβH deficiency, Droxidopa treatment, and the effect on orthostatic tolerance and glucose homeostasis. [8] - May 5, 2020 — Currently on the market there is a prescription medication, called Droxidopa. Droxidopa is a synthetic amino acid that is converted to ... [9] - Treatment options: Droxidopa (See Targeted Therapy.) Fludrocortisone (0.1-0.3 mg daily) provides some benefit, but marked orthostatic hypotension still ...

Differential Diagnosis of Dopamine Beta-Hydroxylase Deficiency

Dopamine beta-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by the inability to produce norepinephrine, a crucial neurotransmitter involved in the regulation of blood pressure and other autonomic functions. When considering differential diagnosis for DBH deficiency, several conditions should be taken into account:

• Primary Autonomic Failure: This condition is characterized by a complete absence of sympathetic noradrenergic function, similar to DBH deficiency [1]. However, primary autonomic failure can also involve parasympathetic dysfunction, which is not typically seen in DBH deficiency.
• Autonomic Dysreflexia Syndrome: This syndrome is often associated with spinal cord injuries and can present with severe orthostatic hypotension, similar to DBH deficiency [9]. However, autonomic dysreflexia syndrome is typically accompanied by other symptoms such as sweating, flushing, and bradycardia.
• Aromatic L-amino Acid Decarboxylase Deficiency: This rare genetic disorder affects the production of dopamine and norepinephrine, similar to DBH deficiency [9]. However, aromatic L-amino acid decarboxylase deficiency is typically associated with other symptoms such as intellectual disability and seizures.
• Spinal Injuries: Spinal injuries can lead to autonomic dysfunction, including orthostatic hypotension, which may be mistaken for DBH deficiency [9].
• Other Rare Genetic Disorders: Several rare genetic disorders, such as familial dysautonomia and congenital insensitivity to pain with anhidrosis, can present with similar symptoms to DBH deficiency.

Key Features to Distinguish DBH Deficiency from Other Conditions

To accurately diagnose DBH deficiency, it is essential to consider the following key features:

• Complete absence of sympathetic noradrenergic function: This is a hallmark feature of DBH deficiency [1].
• Severe orthostatic hypotension: This symptom is often present in DBH deficiency and can be used to distinguish it from other conditions.
• Ptosis: Ptosis, or drooping eyelids, is a characteristic feature of DBH deficiency [5].

References

[1] JM Senard · 2006 · Cited by 57 — Definition/diagnostic criteria​​ Dopamine beta-hydroxylase (DβH) deficiency is a very rare form of primary autonomic failure characterized by a complete absence ...

[3] Sep 26, 2024 — Dopamine beta-hydroxylase (DBH) deficiency is characterized by lack of sympathetic noradrenergic function resulting in profound deficits in ...

[5] Dopamine beta-hydroxylase deficiency presents with infantile or childhood onset noradrenergic failure with orthostatic hypotension and ptosis. Affected ...

[6] by T Wassenberg · 2021 · Cited by 14 — Dopamine beta hydroxylase (DBH) deficiency is an extremely rare autosomal recessive disorder with severe orthostatic hypotension, ...

[8] by JM Senard · 2006 · Cited by 57 — The diagnosis should be suspected when pure sympa- thetic autonomic failure is associated with absence of both noradrenaline and adrenaline and ...