Diseases

Dopamine β-Hydroxylase Deficiency – Causes, Symptoms & Treatment

Dopamine B-hydroxylase deficiency

Dopamine β-hydroxylase deficiency is a very rare inherited disorder characterized by the absence of norepinephrine and adrenaline in the blood . The concentration of dopamine is increased. As a result, the body can no longer adapt to external stressful situations and stress.

What is dopamine β-hydroxylase deficiency?

In addition to an increased concentration of dopamine , a dopamine β-hydroxylase deficiency is also characterized by the lack of the neurotransmitters and hormones norepinephrine and adrenaline . These two hormones are created in the body by converting dopamine. The formation of these hormones takes place in several reaction steps.

In the first step of the reaction, dopamine is oxidized to noradrenaline with the enzymatic assistance of dopamine β-hydroxylase by introducing an additional OH group at the C3 atom. In the process, dopamine reacts with oxygen and ascorbic acid . In addition to noradrenaline, water and dehydroascorbic acid are also formed.

Adrenaline is then formed from noradrenaline by the attachment of a methyl group to the amino group. In the case of a dopamine β-hydroxylase deficiency, the first reaction step does not take place or only takes place insufficiently. The formation of both hormones is prevented. Norepinephrine and adrenaline act as stress hormones .

With increasing physical stress, the organism must quickly activate energy reserves. It does this by rapidly making glucose available from glycogen stores and boosting fat burning. Adrenaline in particular can activate these processes.

Norepinephrine also acts as a neurotransmitter and causes blood vessels to constrict by binding to adrenoceptors. This increases blood pressure. If these stress hormones are missing, the body can no longer react to stress. However, a defective dopamine β-hydroxylase enzyme prevents its formation.

causes

Dopamine β-hydroxylase deficiency is hereditary. This is an autosomal recessive mutation of a gene on chromosome 9, which codes for dopamine β-hydroxylase as the DBH gene. The disease has so far only been observed very rarely. Their frequency is estimated at one in a million.

However, there is also the assumption that the actual prevalence of the disease is in fact significantly higher. In many cases, the embryo dies prenatally. Since the disease is inherited in an autosomal recessive manner, affected individuals must have both parents with the defective gene.

However, because it occurs only once in each of them, the parents do not have dopamine β-hydroxylase deficiency. However, they can transmit the disease to their offspring up to 25 percent.

Symptoms, Ailments & Signs

The symptoms of a dopamine β-hydroxylase deficiency correspond to the loss of the functions of the two hormones norepinephrine and adrenaline. In stressful situations, the body has to mobilize its energy reserves in order to be able to react quickly to stress. In evolution, those organisms that were able to flee or fight quickly in the face of danger always had an advantage.

Even with less dangerous loads, energy reserves must be activated. If this is not successful, the body cannot adapt to stress, because after the energy sources provided have been used up, there are initially no more new ones available. Orthostatic hypotension and various cardiovascular disorders are among the most important symptoms of dopamine β-hydroxylase deficiency.

Orthostatic hypotension is characterized by the fact that those affected tend to experience dizziness , nausea , low blood pressure and circulatory collapse (syncope) when standing. Other symptoms of orthostatic hypotension are blurred vision , unsteadiness, ringing in the ears , headaches , drowsiness, flickering and tunnel vision.

Inner restlessness , pallor , sweating and a feeling of cold often appear . The syncope can lead to serious falls and accidents. Symptoms largely disappear with sitting, lying down, and rest. In addition to orthostatic hypotension, blood pressure is always too low.

Newborns with dopamine β-hydroxylase deficiency also frequently suffer from hypothermia , hypotonia and hypoglycemia . In hypothermia, too little body heat is produced, which can quickly lead to the body cooling down. Muscle hypotonia is characterized by reduced muscle strength.

Since the carbohydrate reserves cannot be activated so quickly either, dangerous hypoglycaemia (low blood sugar) can develop. If left untreated, symptoms progressively worsen in adulthood.

Diagnose

When diagnosing dopamine β-hydroxylase deficiency, it is not sufficient to just measure the dopamine β-hydroxylase enzyme. In about four percent of the population, this enzyme cannot be detected at all, although there is no deficiency.

Dopamine-β-hydroxylase deficiency can only be unequivocally detected by measuring the concentration of dopamine, noradrenaline and adrenaline. If the plasma level of dopamine is increased without noradrenaline and adrenaline being detected, it is clearly a dopamine β-hydroxylase deficiency.

When should you go to the doctor?

Expectant parents who themselves suffer from dopamine β-beta-hydroxylase deficiency and know it should arrange for a prenatal examination. By measuring the levels of dopamine, norepinephrine and adrenaline in the blood, it can be reliably determined whether the deficiency has been passed on to the child.

If this is the case, precautionary measures should be taken before the birth to limit any complications. If the newborn develops a rapid cooling after birth and shows other signs of dopamine β-beta-hydroxylase deficiency, a doctor should still be consulted.

Even with symptoms such as dizziness, nausea and low blood pressure, an early clarification by the family doctor or a specialist is advisable. If the symptoms result in falls or accidents, the emergency doctor must be called immediately.

The same applies to the typically occurring circulatory collapses and signs of increasing cooling. Parents of affected children should also take advantage of psychological support, since the illness is usually just as exhausting for the relatives as it is for the affected child.

Treatment & Therapy

Dopamine β-hydroxylase deficiency can be treated very well with medication. The drug DOPS or Droxipoda is administered orally two to three times a day. This active ingredient is a so-called prodrug. It is structured like noradrenaline and already contains the important OH group on the C3 atom. The enzyme dopamine β-hydroxylase is therefore superfluous.

A carboxyl group is still attached to the end of the molecule of this active ingredient. The carboxyl group is then split off in the body with the direct formation of noradrenaline. Since adrenaline is formed from noradrenaline, its formation is then also secured. Lifelong use of this drug allows you to lead a largely normal life. There is still no evaluable data on the long-term prognosis of the disease.

Outlook & Forecast

Self-healing does not occur in the case of a dopamine β-hydroxylase deficiency. This disease must therefore be treated by a doctor in any case.

If the dopamine β-hydroxylase deficiency is not treated, the affected person cannot react properly in stressful situations. This leads to circulatory problems, high blood pressure and, in the worst case, a heart attack . Likewise, many patients suffer from severe headaches, dizziness and rushing.

This deficiency severely limits the quality of life of those affected and can lead to difficulties in everyday life. Muscle problems also occur if the disease is not treated. If, in addition to the dopamine β-hydroxylase deficiency, there is also hypoglycaemia, this can lead to a loss of consciousness. The symptoms usually get worse with age.

Dopamine β-hydroxylase deficiency is treated with medication. The symptoms are completely relieved and there are no special complications. Since the disease cannot be cured causally, patients are dependent on taking the medication for life. Due to the lack of data on this disease, no long-term prognosis can be given. However, early treatment does not negatively affect the life expectancy of the patient.

prevention

Since dopamine β-hydroxylase deficiency is a hereditary disease, no recommendations for prevention can be given. If cases of this disease have already occurred in the family or relatives, human genetic counseling can be used. If both parents have the defective gene, the offspring has a 25 percent chance of having dopamine β-hydroxylase deficiency due to autosomal recessive inheritance.

aftercare

In the case of dopamine β-hydroxylase deficiency, follow-up measures are extremely limited. As a rule, those affected are first dependent on correct and early treatment by a doctor so that there are no further symptoms or complications. Only after proper treatment should the triggers of the disease be avoided as far as possible.

Since complete healing of the dopamine β-hydroxylase deficiency is not possible in most cases, the affected person is dependent on lifelong therapy. In most cases, sufferers of dopamine β-hydroxylase deficiency must take medication. The intake itself is usually two or three times a day and should be followed as prescribed by the doctor.

It is always important to pay attention to the correct dose. In case of doubt or in the event of various ambiguities, a doctor should always be consulted in the event of a dopamine β-hydroxylase deficiency. In most cases, taking this drug can lead to an ordinary life, so there are no special restrictions.

In the case of dopamine-β-hydroxylase deficiency, it is not uncommon for contact with other people affected by the disease to be useful. This often leads to an exchange of information, which can make everyday life easier for those affected. The life expectancy of the patient is usually not negatively affected by the disease.

You can do that yourself

Dopamine beta-hydroxylase deficiency is a very rare form of primary autonomic dysfunction that is inherited. The patient cannot take self-help measures to treat the disease causally. Couples in whose families a dopamine β-hydroxylase deficiency has already occurred can take advantage of human genetic counseling if they intend to start a family.

Carriers of the defective gene that causes dopamine beta-hydroxylase deficiency do not have to have the disorder themselves to pass it on. If only one parent is affected, there is no risk for the offspring. However, if both parents are carriers of the defective gene, the risk of their offspring inheriting the disease is 25 percent.

To make matters worse, miscarriages often occur in the case of such pregnancies , since the disease already leads to the death of the embryo before birth. Affected couples should therefore carefully consider whether they want to father a child together.

Dopamine beta-hydroxylase deficiency can be treated with lifelong medication. Many patients are then largely symptom-free. It is therefore an important step towards self-help if you suspect this rare disease to consult a doctor immediately. If the disorder has already occurred in the family, the doctor treating you must be informed of this.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.