Introduction to Dopamine β-hydroxylase Deficiency

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

What is dopamine β-hydroxylase deficiency?

According to DigoPaul, a dopamine-β-hydroxylase deficiency is characterized not only by an increased concentration of dopamine but also by a lack of neurotransmitters and hormones noradrenaline and adrenaline. These two hormones are created in the body when dopamine is converted. The formation of these hormones takes place in several reaction steps.

In the first reaction step, dopamine is oxidized to norepinephrine with the help of the enzymatic support of dopamine-β-hydroxylase with the addition of an additional OH group on the C3 atom. Dopamine reacts with oxygen and ascorbic acid. In addition to noradrenaline, water and dehydroascorbic acid are also formed.

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

With increasing physical stress, the organism must quickly activate energy reserves. This happens through the rapid supply of glucose from the glycogen stores and through the stimulation of fat burning. Adrenaline in particular can activate these processes.

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

Causes

The dopamine-β-hydroxylase deficiency is hereditary. This is an autosomal recessive mutation of a gene on chromosome 9, which encodes dopamine β-hydroxylase as the DBH gene. The disease has only been observed very rarely so far. 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, both parents must have the defective gene in the affected person.

Because it only occurs once in each of them, the parents do not suffer from dopamine β-hydroxylase deficiency. However, up to 25 percent of the disease can be passed on to their offspring.

Symptoms, ailments & signs

The symptoms of a dopamine-β-hydroxylase deficiency correspond to the failure of the functions of the two hormones noradrenaline 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 were always at an advantage, which could quickly adapt to flight or fight in case of danger.

Even with less dangerous loads, energy reserves must be activated. If this does not succeed, the body cannot adapt to stress, as there are initially no more new ones available after the energy sources provided have been used up. 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, headache, drowsiness, flickering eyes and tunnel vision.

Often there are inner restlessness, paleness, sweating and a feeling of coldness. The syncope can lead to serious falls and accidents. The symptoms largely go away when you sit down, lie down, and rest. In addition to orthostatic hypotension, blood pressure is always too low.

In addition, newborns with dopamine β-hydroxylase deficiency often suffer from hypothermia, muscle hypotension and hypoglycaemia. With hypothermia, too little body heat is produced, which can quickly lead to the organism cooling down. Muscle hypotonia is characterized by decreased muscle strength.

Since the carbohydrate reserves cannot be activated as quickly either, dangerous hypoglycemia (low blood sugar) can develop. If left untreated, symptoms continue to worsen in adulthood.

Diagnosis

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

The unambiguous detection of the dopamine-β-hydroxylase deficiency is only possible by measuring the concentration of dopamine, noradrenaline and adrenaline. If the plasma level of dopamine is increased without noradrenaline and adrenaline can be detected, there is clearly a dopamine-β-hydroxylase deficiency.

When should you go to the doctor?

Expectant parents who know this themselves from a dopamine-β-beta-hydroxylase deficiency should arrange for a prenatal examination. By measuring the levels of dopamine, noradrenaline and adrenaline in the blood, it is possible to reliably determine whether the deficiency was 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 becomes cold rapidly after birth and shows other signs of dopamine-β-beta-hydroxylase deficiency, a doctor should still be consulted.

If you have symptoms such as dizziness, nausea and low blood pressure, it is advisable to have an early diagnosis by your family doctor or a specialist. If the complaints lead to falls or accidents, the emergency doctor must be called immediately.

The same applies to the typical circulatory breakdowns and signs of increasing cooling. Parents of affected children should also seek psychological support, as the illness is usually just as exhausting for relatives as it is for the affected child.

Treatment & Therapy

The 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 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 arises from noradrenaline, its formation is also ensured. Lifelong use of this drug allows for a largely normal life. No evaluable data are yet available for the long-term prognosis of the disease.

Outlook & forecast

With a dopamine-β-hydroxylase deficiency there is no self-healing. This disease must therefore be treated by a doctor in any case.

If the dopamine β-hydroxylase deficiency is not treated, the person affected will not be able to 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 being rushed.

This deficiency extremely restricts the quality of life of the person affected and can lead to difficulties in everyday life. Muscle discomfort can also occur if the condition is not treated. If, in addition to the dopamine-β-hydroxylase deficiency, hypoglycaemia should occur, this can lead to a loss of consciousness. The symptoms usually worsen with increasing age.

Dopamine β-hydroxylase deficiency is treated with the help of medication. The symptoms are completely alleviated and there are no particular complications. Since the cause of the disease cannot be cured, 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, genetic counseling can be used. If both parents have the defective gene, the offspring has a 25 percent chance of suffering from a dopamine β-hydroxylase deficiency due to the autosomal recessive inheritance.

Aftercare

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

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

It is always important to ensure that the dose is correct. In case of doubt or if anything is unclear, a doctor should always be consulted with a dopamine-β-hydroxylase deficiency. In most cases, an ordinary life can be made possible by taking this drug, so there are no particular restrictions.

It is not uncommon for people who have dopamine β-hydroxylase deficiency to have contact with other people affected by the disease. This often leads to an exchange of information, which can make everyday life easier for the person concerned. The life expectancy of the patient is also 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 hereditary. The patient cannot take self-help measures to treat the cause of the disease. Couples in whose families a dopamine β-hydroxylase deficiency has already occurred can take advantage of genetic counseling if they intend to start a family.

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

A further complicating factor is that such pregnancies often lead to miscarriages, since the disease leads to the death of the embryo prenatally. 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 see a doctor immediately. If the disorder has already occurred in the family, the attending physician must be informed of this.

Dopamine β-hydroxylase Deficiency