Dopamine beta hydroxylase deficiency



Dopamine beta (β)-hydroxylase deficiency is a condition involving inadequate dopamine beta-hydroxylase. 



Characterized by increased amounts of serum dopamine and the absence of norepinephrine and epinephrine. 



Dopamine beta (β)-hydroxylase deficiency affects the autonomic nervous system (ANS). 



The ANS works via two opposing branches, the sympathetic and parasympathetic, both of which antagonistically control involuntary processes that regulate bodily homeostasis. 



It is an autosomal recessive disorder caused by a mutation in the DβH gene, which results in the production of a nonfunctional dopamine β-hydroxylase enzyme.



Dopamine released, acts as false neurotransmitter, in place of norepinephrine. 



Dopamine beta hydroxylase is the enzyme responsible for converting dopamine to norepinephrine.



Dopamine beta-hydroxylase deficiency is a very rare form of dysautonomia. 



A rare diseases, with a prevalence of fewer than 20 affected individuals, all of whom are of Western European descent.



Without this enzyme signs and symptoms: 



Initial onset of  DβH deficiency manifestations often first appear as complications shortly after birth: vomiting, dehydration, hypotension, muscle hypotonia, hypothermia, and hypoglycemia.



Individuals affected by dopamine β-hydroxylase deficiency may present with droopy eyelids, nasal congestion, and hypotension. 



Orthostatic hypotension is the most common complaint of individuals with dopamine β-hydroxylase deficiency.



Orthostatic hypotension symptoms are: dizziness, blurred vision, or fainting upon standing. 



DβH deficiency patients may have an inability to stand for a prolonged period of time. 



Symptoms are pronounced when going from supine to upright positions, such as getting out of bed in the morning. 



DβH deficiency symptoms are worsened by extreme climates due to loss of fluid through excessive sweating. 



DβH deficiency patients are unable  to maintain normal blood pressure, making it difficult for people with DβH deficiency to exercise.



Males with DβH deficiency may experience retrograde ejaculation: due to dysmotility of smooth muscle of the bladder, which as innervated by the ANS. 



There is a subset of DβH deficiency patients with hypermobility, in the form of  Ehlers Danlos syndrome, which is also associated with postural orthostatic tachycardia syndrome, another form of dysautonomia.



Hypoglycemia, which is thought to be caused by adrenomedullary failure is common.



A loss of noradrenergic control is seen as T-wave abnormalities on electrocardiogram. 



Prolactin is frequently suppressed by excessive dopamine found in the patient’s central nervous system. 



Excessive dopamine can produce  vomiting and inhibiting motor signaling to the GI tract.



Untreated patients with DβH deficiency should avoid hot environments, strenuous exercise, standing still for prolonged time, dehydration, and rapid change of position from horizontal to upright.



In  DβH deficiency, L-Threo-DOPS, a synthetic precursor of noradrenaline, administration has proven effective in dramatic increase of blood pressure and subsequent relief of postural symptoms.



L-DOPS has an ability to increase the levels of central nervous system norepinephrine. 



L-threo-DOPS is very effective for restoring noradrenergic tone and correcting postural hypotension, but it’s response to treatment is variable and the long-term and functional outcome is unknown.



L-DOPS helpful in treating a variety of other conditions related to hypotension: 



Diabetes induced orthostatic hypotension



Dialysis-induced hypotension



Orthostatic intolerance



Familial amyloidotic polyneuropathy



Spinal Cord Injury 



Additional medications that can help  symptoms: 



phenylpropanolamine- due to pressor response to vascular α-adrenoceptors






Vitamin C a required cofactor for the Dopamine beta hydroxylase enzyme. 



L-threo-DOPS has been described as being “very effective for restoring noradrenergic tone and correcting postural hypotension, response to treatment is variable and the long-term and functional outcome is unknown.



The perinatal period is marked by inadequacy of the autonomic nervous system to control blood pressure, blood sugar, and body temperature. 



Patients experiences orthostatic hypotension, exercise intolerance, and the morbidity related to falls and syncope





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