Dopamine-β-hydroxylase deficiency represents a very rare hereditary disorder characterized by the absence of norepinephrine and epinephrine 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 absence of the neurotransmitters and hormones norepinephrine and epinephrine. These two hormones are produced in the body by the conversion of dopamine. The formation of these hormones occurs 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 insertion of an additional OH group at the C3 atom. In this process, dopamine reacts with oxygen and ascorbic acid. In addition to norepinephrine, water and dehydroascorbic acid are formed. Adrenaline is then formed from norepinephrine by the bonding of a methyl group to the amino group. In dopamine-β-hydroxylase deficiency, the first reaction step does not occur or occurs inadequately. The formation of the two hormones is prevented. Norepinephrine and epinephrine function as stress hormones. When physical stress increases, the organism must quickly activate energy reserves. This is done by rapidly providing glucose from glycogen stores and by 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 respond to stress. However, a defective enzyme dopamine-β-hydroxylase prevents their formation.
Causes
Dopamine-β-hydroxylase deficiency is hereditary. It involves an autosomal recessive mutation of a gene on chromosome 9, which is the DBH gene encoding dopamine-β-hydroxylase. The disease has been observed very rarely. Thus, its frequency is estimated at one in a million. However, there is also the assumption that the actual prevalence of the disease is in fact much higher. This is because in many cases, death of the embryo already occurs prenatally. Since the disease is inherited in an autosomal recessive manner, both parents of affected individuals must possess the defective gene. However, because it occurs only once in each of them, the parents do not suffer from dopamine-β-hydroxylase deficiency. They can, however, pass the disease on to their offspring at a rate of 25 percent.
Symptoms, complaints, and signs
The symptoms of dopamine-β-hydroxylase deficiency correspond to the failure of the functions of the two hormones norepinephrine and epinephrine. In stressful situations, the body must mobilize energy reserves to respond quickly to stress. In evolution, organisms that could quickly prepare for flight or fight in the face of danger have always had an advantage. Even under less dangerous stresses, energy reserves must be activated. If this is not successful, the body cannot adjust to stresses, because after the provided energy sources have been used up, there are initially no new ones available. Thus, orthostatic hypotension and various cardiovascular disorders are among the most important symptoms of dopamine-β-hydroxylase deficiency. Orthostatic hypotension is characterized by a tendency for sufferers to experience dizziness, nausea, low blood pressure, and circulatory collapse (syncope) when standing. Other symptoms of orthostatic hypotension include blurred vision, inability to stand, ringing in the ears, headache, lightheadedness, flickering eyes and tunnel vision. Internal agitation, pallor, sweating and chills are often evident. Syncope can lead to serious falls and accidents. Symptoms largely disappear on sitting down, lying down, and rest. In addition to orthostatic hypotension, blood pressure is always too low. Newborns with dopamine-β-hydroxylase deficiency further often suffer from hypothermia, muscle hypotonia, and hypoglycemia. In hypothermia, too little body heat is produced, and cooling of the organism can occur rapidly. 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 not treated, symptoms become progressively worse in adulthood.
Diagnosis
When diagnosing dopamine-β-hydroxylase deficiency, it is not sufficient to determine only the enzyme dopamine-β-hydroxylase. In approximately four percent of the population, this enzyme cannot be detected at all, even though there is no deficiency. Clear evidence of dopamine-β-hydroxylase deficiency can only be obtained by measuring the concentration of dopamine, norepinephrine and epinephrine. If the plasma level of dopamine is elevated without detection of norepinephrine and epinephrine, the deficiency is clearly dopamine-β-hydroxylase deficiency.
When should you see a doctor?
Expectant parents who themselves have dopamine-β-beta-hydroxylase deficiency and know it should arrange for prenatal testing. Measurement of the levels of dopamine, norepinephrine, and epinephrine in the blood can reliably determine whether the deficiency has been passed on to the child. If this is the case, precautions should be taken before birth to limit any complications. If the newborn cools rapidly after birth and shows other signs of dopamine-β-beta-hydroxylase deficiency, a physician should still be consulted. Early clarification by the family doctor or a specialist is also advisable for symptoms such as dizziness, nausea and low blood pressure. If the symptoms lead to 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 seek psychological support, as the disease is usually just as debilitating for relatives as it is for the affected child.
Treatment and therapy
Dopamine-β-hydroxylase deficiency can be treated very well with medication. This involves oral administration of the drug DOPS or Droxipoda two to three times daily. This active ingredient is a so-called prodrug. It is structured like norepinephrine 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 molecular end of this active ingredient. In the body, the carboxyl group is then cleaved off to form norepinephrine directly. Since epinephrine is formed from norepinephrine, its formation is then also assured. The lifelong use of this drug allows a largely normal life. No evaluable data are yet available on the long-term prognosis of the disease.
Outlook and prognosis
In dopamine-β-hydroxylase deficiency, self-healing does not occur. Therefore, this condition must be treated by a physician in any case. If dopamine-β-hydroxylase deficiency is not treated, the affected person cannot react properly in stressful situations. Circulatory problems, high blood pressure and, in the worst case, a heart attack therefore occur. Many patients also suffer from severe headaches, dizziness and hyperacusis. This deficiency extremely limits the quality of life of the affected person and can lead to difficulties in everyday life. Muscle complaints also occur if the disease is not treated. Should hypoglycemia occur in addition to dopamine-β-hydroxylase deficiency, it can lead to a loss of consciousness. In this case, the symptoms usually intensify with increasing age. Treatment of dopamine-β-hydroxylase deficiency is carried out with the help of medication. The symptoms are completely alleviated and no particular complications occur. Since the disease cannot be cured causally, patients are dependent on taking the medication for the rest of their lives. Due to the lack of data on this disease, no long-term prognosis can be given. However, if treated early, the patient’s life expectancy will not be negatively affected.
Prevention
Because dopamine-β-hydroxylase deficiency is a hereditary disease, no recommendations can be made for prevention. If cases of this disorder have already occurred in the family or relatives, human genetic counseling can be sought. If both parents possess the defective gene, there is a 25 percent chance that the offspring will suffer from dopamine-β-hydroxylase deficiency due to autosomal recessive inheritance.
Aftercare
In dopamine-β-hydroxylase deficiency, the measures of follow-up care are extremely limited. As a rule, affected individuals first rely on proper and early treatment by a physician to prevent further symptoms or complications. Only after proper treatment should the triggers of the disease be avoided as much as possible. Since a complete cure of dopamine-β-hydroxylase deficiency is not possible in most cases, the affected person is dependent on lifelong therapy. In most cases, those affected with dopamine-β-hydroxylase deficiency must take medication. The medication itself is usually taken two or three times a day and should be taken as prescribed by the doctor. It is always necessary to pay attention to the correct dose. In case of doubt or various ambiguities, a doctor should always be consulted in case of dopamine-β-hydroxylase deficiency. In most cases, taking this medication can allow for an ordinary life, so there are no particular limitations. Not infrequently, in the case of dopamine-β-hydroxylase deficiency, contact with other sufferers of the disease can also be useful. This often leads to an exchange of information, which can make the daily life of the affected person easier. The patient’s life expectancy is also usually not negatively affected by the disease.
What you can do 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 disease causally. Couples in whose families dopamine-β-hydroxylase deficiency has already occurred may seek human genetic counseling if the intention is to start a family. Carriers of the defective gene that causes dopamine beta-hydroxylase deficiency do not have to have the disorder themselves to inherit it. If only one parent is affected, there is no risk to the common offspring. However, if both parents are carriers of the defective gene, the risk for the common offspring to inherit the disease is 25 percent. To make matters worse, such pregnancies often result in miscarriages, as the disease leads to the death of the embryo already prenatally. Affected couples should therefore carefully consider whether they want to father a child together. Dopamine-beta-hydroxylase deficiency can be treated by lifelong medication. Many patients are then largely free of symptoms. It is therefore an important self-help step to consult a doctor immediately if this rare disease is suspected. If the disorder has already occurred once in the family, it is essential to inform the attending physician.
