Enzymes are involved in almost every bodily process and especially in the metabolism of an organism. In a genetic or acquired enzyme defect, the biochemical activity of the affected enzymes changes, often resulting in enzymopathy. Some enzyme defects and deficiencies can now be compensated for with enzymatic substitution, which usually has to be carried out throughout life.
What is an enzyme defect?
An enzyme defect is present whenever an enzyme is impaired in its biochemical activity due to structural changes. Enzymes are characterized by biochemical activity. They are substances consisting of giant biological molecules with a catalytic function in chemical reactions. In the human body, innumerable reactions take place on a biochemical basis. As catalysts, enzymes accelerate the course of these reactions or even ensure that certain reactions take place in the human body in the first place. Almost all enzymes consist of proteins. The catalytically active RNA is an exception to this. In all other cases, the formation of enzymes in the cell takes place within the framework of protein biosynthesis by the ribosomes. In the metabolism of all organisms, enzymes perform irreplaceable tasks and control the vast majority of all biochemical reactions. Some structural changes of enzymes lead to disturbances or even completely abolish the biochemical activity of the enzyme. As a consequence of an enzymatic defect, the formation of the enzymatically catalyzed synthesis products is affected by disturbances. This means that the synthesis products from the catalyzed reactions of the defectively structured enzyme are only available in the organism to a reduced extent or not at all. In addition to a faulty enzyme structure, the misdirected provision of an enzyme in organic metabolism can also cause an enzyme defect. In this case, it is not the quality but the quantity of an enzyme that disturbs its biochemical activities. The symptoms of an enzyme defect are summarized as enzymopathies.
Causes
A majority of all enzyme defects are congenital and result from genetic causes. For example, mutations in DNA can affect genes that code for one or more of the enzymes or carry coding for substances involved in enzyme biosynthesis. In this way, a mutation can lead, for example, to the assembly of a particular enzyme with the wrong structure. Enzyme deficiency or even the complete absence of certain enzymes in the human organism can also be due to mutations. In adrenogenital syndrome, for example, there is a hereditary enzyme defect of 21-beta-hydroxylase. Meanwhile, a mutation-related enzyme deficiency underlies favism. In this hereditary disease, the defect is on glucose-6-phosphate dehydrogenase. Some enzyme defects are autosomal dominant, others autosomal recessive, and still others X-linked. In exceptional cases, mutation-related enzyme defects also occur in the context of sporadic processes and in this case are not referred to as inherited mutations but as new mutations. Depending on the enzymes affected, an enzyme defect leads to different symptoms. Enzymopathies are always metabolic diseases caused either by enzyme deficiency, enzyme excess, or congenital or acquired structural defects of enzymes.
Symptoms, complaints, and signs
In most cases, enzyme defects result from incorrectly encoded amino acid sequences of DNA. However, this faulty coding does not necessarily cause symptoms. Some patients with enzyme defects remain asymptomatic throughout their lives. Whether an enzyme defect leads to an enzymopathy with signs of disease depends on the one hand on the enzyme affected and on the other hand on the extent of its activity alteration. Enzyme defects of the most important key enzymes essentially all lead to severe disturbances of various body functions and in most cases appear prenatally. Particularly severe enzyme defects trigger abortion. This means that the human being is not viable after a certain loss of function of various enzymes. The consequence of enzyme defects is also often idiosyncrasy or severe developmental delay. Due to their roles in metabolism, metabolic and hormonal disorders are sometimes the most common manifestations of enzyme defects.The most common metabolic disorder of newborns is phenylketonuria (PKU), which is also due to an enzymatic defect, for example.
Diagnosis
Enzyme defects are usually diagnosed by enzymatic analysis or are diagnosed by genetic diagnosis. The prognosis of patients is strongly related to the enzyme affected and the extent of its activity alteration. While some enzyme defects cause no symptoms, others have a lethal course.
Complications
Enzyme defect can cause various complications. In general, enzyme defects can appear prenatally and cause serious disorders of various bodily functions. In particularly severe cases during pregnancy, the child may even be aborted. Mild defects result in developmental disorders, which are sometimes felt throughout the life of the affected person. In addition, metabolic and hormonal disorders may occur. A disturbed metabolism sometimes also causes an unpleasant body odor in the affected person. So-called phenylketonuria is particularly common, and several complications can occur. There is an increased risk of mental abnormalities, which can extend to mental retardation of the child. Affected children suffer more frequently from epileptic seizures, disturbed muscle tension and spastic twitching during childhood. In most cases, there is also increased irritability, which can develop into severe psychological disorders in the course of time. Externally, PKD is manifested by a light skin color with blond hair and blue eyes. Rarely, severe pigmentation disorders occur. Therapy for an enzyme defect usually does not result in severe complications.
When should you see a doctor?
A visit to the doctor is necessary as soon as disorders or irregularities of the metabolism become apparent. If a growing child is found to have a developmental disorder, a medical examination should take place. Since an enzyme defect can have a fatal course in severe cases, a doctor should be consulted in good time in the event of complaints in various areas. If there is pain or restrictions in the functioning of different systems, a doctor is needed. In case of hormonal problems, mood swings or weight problems, a doctor should be consulted. If abdominal pain, complaints of the cardiovascular system, sleep disturbances or a general feeling of malaise set in, a doctor is needed. If mental abnormalities occur, there is reason for concern. Apathy, depressive phases or listlessness should be discussed with a doctor if they continue unabated for several weeks. A doctor should be consulted in the event of cramps, sensory disturbances, a general feeling of illness, fever or impaired consciousness. If irritability increases in everyday life, it is advisable to talk to a doctor about the observation. If blood is repeatedly noticed in the urine or stool when going to the toilet, a visit to the doctor is necessary. An inner restlessness, decreased performance level and concentration problems, should be examined and treated by a doctor. If changes occur in the appearance of the skin or if there is a disturbance in hair growth, a visit to the doctor is necessary. A pigment disorder, swelling of the skin or discoloration should be investigated.
Treatment and therapy
In most cases, enzymatic defects are congenital and therefore cannot be cured until gene therapy treatment approaches reach the clinical stage. Symptomatic treatment, to the extent possible, consists of so-called enzyme substitution. This therapeutic approach is a rather newer procedure and corresponds to the supply of the missing enzymes from the outside. In the case of genetic defects, the substitution must be carried out throughout the patient’s life. With the supply of structurally sound enzymes, the organism can again catalyze the appropriate reactions to a sufficient degree. Loss of enzyme function can be compensated for in this way. In the case of acquired enzyme defects or enzyme deficiencies in the context of pancreatic insufficiency, for example, acid-stable digestive enzymes must be substituted. Not all enzyme defects can be compensated for by enzyme substitution. For example, if certain enzymes are produced in excess, substitution makes little sense accordingly. Enzyme deficiencies cannot always be treated by substitution either. In these cases, treatment is purely symptomatic.
Outlook and prognosis
The enzyme defect is a congenital or acquired disease that cannot be cured at the current state of scientific knowledge. For legal reasons, the genetic mutation cannot be changed, so the patient must live with impairments for life. Nevertheless, treatment of the individual symptoms is possible in most cases due to the available medical options. The metabolic disorder is treated very successfully in a long-term therapy. There are only a few restrictions in everyday life. If treatment of the enzyme defect is refused, a sudden termination of pregnancy or a developmental disorder of the child can be expected in the case of a hereditary defect. Adults suffer lifelong from physical problems such as muscle complaints or mental illness. General performance is reduced and participation in social life is limited due to poor well-being. If medical care is initiated, the patient’s health improves considerably. Enzyme substitution takes place. The affected person must participate in regular examinations to correct imbalances and optimize dosage. In addition, a healthy lifestyle and a balanced diet improve the patient’s health. If harmful substances such as alcohol, nicotine or other stimulants are avoided, the affected person can achieve a good quality of life without significant limitations despite the enzyme defect. As soon as treatment is discontinued, relapse occurs.
Prevention
Genetic enzyme defects can be prevented to a certain extent in the context of genetic counseling during the family planning phase. At-risk couples may thus be able to decide against having children of their own, for example.
Follow-up
Since the enzyme defect is a congenital and therefore also hereditary disease, no complete cure can be achieved. The symptoms can only be treated purely symptomatically and not causally, so the affected person is usually dependent on lifelong therapy. This means that no special aftercare measures are available to the affected person. The main focus of this therapy is also the early detection of the enzyme defect, so that further complications or a worsening of the symptoms do not occur. In order to prevent the recurrence of the enzyme defect in the descendants, genetic testing and counseling can also be performed if the patient wishes to have children. The measures for the treatment of this disease depend very much on the exact nature and expression of this defect, so that no general prediction can be made here. Those affected are usually dependent on the help of their family and friends in everyday life. Psychological support can also be very useful, whereby not only the affected persons themselves, but also their parents are often dependent on psychological treatment. Whether and how the enzyme defect will reduce the life expectancy of the affected person cannot be predicted in general.
Here’s what you can do yourself
The self-healing powers are unable to cure the congenital enzyme defect by themselves. The patient has no means to achieve a cure of the disease by self-help. The missing enzymes must be provided to the organism at regular intervals. To prevent the symptoms, the affected person can repeatedly apply light protection ointments to the skin. He can do this daily on his own responsibility and without a fixed dosage. The ointments should be tested for tolerance and have a high sun protection factor. Direct sunlight should always be avoided. The patient should wear clothing that covers all parts of the body well and is not translucent. The better the protection, the fewer skin changes occur. In addition, good headgear and the wearing of sunglasses are recommended. If possible, especially in the summer months, the apartment should be left either before sunrise or only after sunset. In case of itching, scratching and rubbing should be avoided under all circumstances. This further aggravates the symptoms. In addition to skin care and protection, mental stabilization is particularly important. Participation in social life or planning leisure activities should not be neglected under any circumstances.Despite the disease, enjoyment of life can be promoted and quality of life maintained.