Maple syrup disease is a rare autosomal recessive enzyme defect that leads to degradation disorders in certain branched-chain amino acids. With early diagnosis and initiation of therapy, affected children exhibit largely normal development.
What is maple syrup disease?
Maple syrup disease is a rare autosomal recessive enzyme defect that leads to degradation disorders in certain branched-chain amino acids. Maple syrup urine disease is a genetic metabolic disorder in the breakdown of the three branched-chain amino acids leucine, isoleucine and valine, which is inherited via autosomal recessive inheritance. As a result of the defect, these three amino acids accumulate to a greater extent in the body fluids and cause the symptoms characteristic of maple syrup disease, such as weak drinking in the newborn, vomiting, impaired muscle activity (muscle hypotonia, opisthotonus), respiratory disorders (metabolic encephalopathy) as well as seizures and coma. In addition to the frequently occurring classic form of maple syrup disease, other forms are differentiated depending on the severity of the metabolic disorder and the resulting enzyme activity. For example, in the intermediate variant, symptoms do not manifest until infancy and are attenuated. The so-called intermittent form of maple syrup disease develops symptomatically primarily during intercurrent infections (with fever, diarrhea, or vomiting), surgery, or as a result of excessive dietary protein intake.
Causes
Maple syrup disease is inherited in an autosomal recessive manner and is caused by various defects in the so-called branched-chain alpha-keto acid dehydrogenase complex, a multienzyme complex. As a result of these defects, there is a deficiency or reduced activity of this multienzyme complex, which causes a degradation disorder of the amino acids leucine, isoleucine and valine. As a result, these and their corresponding alpha-keto acids accumulate in the body tissue and in the body fluids such as blood and urine of the affected person and lead to pronounced neurological symptoms. Also characteristic is a sweetish body and urine odor reminiscent of maple syrup, for which the substance compound sotolone (the most important odor component in lovage and fenugreek), synthesized in isoleucine intermediate metabolism, is responsible.
Symptoms, complaints, and signs
Children suffering from maple syrup disease refuse to eat. As a result, weight loss occurs relatively quickly, including mental deficits and physical symptoms such as sunken eye sockets. Externally, the disease is also manifested by muscle stiffness and cramps. Affected infants also suffer from nausea and vomiting. Many children cry or appear apathetic. This apathy increases as the disease progresses and may indicate severe maple syrup sickness. However, the most characteristic symptom is the sweetish odor of the urine. The urine odor is reminiscent of maple syrup, for which the excessive sugar content in the urine is responsible. Furthermore, weakness in drinking occurs with the disease. Dehydration occurs, which can be recognized by leathery skin, sunken face and other external signs. Typical symptoms of fluid deficiency are fatigue and numbness. Furthermore, maple syrup disease can cause a so-called opisthotonus, a spasm in the extensor muscles of the back, which is accompanied by severe pain and loss of function. The disease is fatal in many cases and is associated with a variety of complaints that increase in intensity as it progresses. Based on the typical urine odor, maple syrup disease can usually be clearly diagnosed.
Diagnosis and course
In addition to the symptoms, which manifest at different ages depending on the form of the disease, maple syrup disease is diagnosed on the basis of increased concentrations of the affected amino acids leucine, isoleucine, and valine and the corresponding alpha-keto acids in blood and urine. The diagnosis is confirmed by the detection of allo-isoleucine as a specific indicator of maple syrup disease in serum and urine.In addition, a pronounced ketoacidosis (metabolic form of acidosis) and hypoglycemia (lowered blood glucose level) can be detected in maple syrup disease, especially in catabolic crises. The elevated concentrations are generally detected by tandem mass spectrometry, a laboratory test method for determining the mass of molecules present in serum or urine. With early diagnosis and timely initiation of therapy, the presence of maple syrup disease can, according to current knowledge, allow the affected child to develop almost normally. If left untreated, maple syrup disease leads to disorders of mental development as well as of the cerebrum.
Complications
Maple syrup disease or leucinosis is a genetic metabolic disorder or enzyme defect. This already appears in infants and young children with corresponding symptoms. As a more frequent complication, an intermittent form of this disease can be triggered by an infection. Similarly, surgery or a diet too rich in protein can trigger such sequelae. As a consequence of the increased risks, patients must be closely monitored in all catabolic crises caused by infections, surgery or other stressful situations. If necessary, acute treatments with glucose or insulin nutrition solutions must be given. Dialysis may also become necessary. The usual therapy of maple syrup disease aims at stabilizing or normalizing the measured values of three disease-causing amino acids. Stabilization of maple syrup disease is achieved by a lifelong diet with greatly reduced protein content. In the event of complications in the course of the disease, however, it may be necessary in individual cases to perform a liver transplant. For this to be necessary, however, other diseases must be present that call into question the attainability of the therapy goals. A further complication of the disease arises as a result of the prescribed low-protein diet. The drastic reduction of protein-containing foods leads to a deficiency of amino acids. These represent the most important building blocks of life. However, this complication can be prevented by specialized nutritional supplementation. It is important that the prescribed amino acid supplements remain free of leucine, isoleucine as well as valine.
When should you go to the doctor?
Maple syrup disease, as a hereditary condition with numerous and serious effects, is definitely worthy of observation. Immediately after birth, professional medical care is inevitable, because otherwise the infant will die. The disease is usually diagnosed by the typical signs, especially the sweetish urine odor. For those affected with maple syrup disease, lifelong medical care is imperative, depending on the course and severity of the mutation. Only the thiamine-dependent variant of Maple syrup urine disease does not require a lifelong low-protein diet to avoid certain proteins. Whether physicians consider liver transplantation even in affected very young children is a matter for consideration. Above all, there are not enough suitable transplants available. Therefore, classical treatment through a medically supervised low-protein diet is the most commonly chosen alternative. In addition, other treatment options usually become necessary. These require close and lifelong medical care of the leukocyanosis patients. International researchers are currently searching for more suitable and less burdensome treatment methods to give people affected by maple syrup disease a better quality of life. Even harmless infections in children must be under medical observation. Crucial for a crisis-free life is the optimal balance of branched-chain amino acids. With optimal medical care, affected individuals have a normal life expectancy.
Treatment and therapy
Therapeutic measures in maple syrup disease are aimed at stabilizing and normalizing the concentrations of branched-chain amino acids through a lifelong diet, administration of the cofactor thiamine (vitamin B1), or liver transplantation, although the latter is used only in very isolated cases and in the presence of other diseases. A small proportion of those affected by maple syrup disease respond to the administration of high-dose thiamine, which can suppress the symptoms of maple syrup disease in the long term.In addition, a lifelong protein-restrictive (low-protein) diet is indicated in the case of maple syrup disease, in which the branched-chain amino acids in particular are dispensed with. In order to compensate for the resulting lack of essential amino acids, these must be supplemented by special leucine-, isoleucine- and valine-free amino acid mixtures, which are usually enriched with trace elements, vitamins and minerals at the same time. For affected newborns or infants, dietary products for the bottle are offered for this purpose, which are prepared with boiled water. To monitor the success of the therapy, the blood values, especially the leucine concentration, are checked regularly. In addition, those affected by maple syrup disease must be given acute infusions (glucose, insulin nutrition solutions) and, if necessary, dialysis (blood exchange transfusions) during catabolic crises resulting from infections, surgery, or other stressful or stressful situations to prevent damage to the brain.
Outlook and prognosis
Maple syrup disease causes a variety of symptoms and signs. However, with early treatment, sequelae can be avoided, resulting in ordinary child development. As a rule, a refusal of food occurs. This complaint can develop into underweight or malnutrition, which can cause damage to the entire body. The patient appears tired and apathetic. Weakness in drinking also occurs, so it is not uncommon for maple syrup disease to cause dehydration of the body. These complaints hinder the growth and development of the child enormously. Furthermore, seizures and pain in the muscles occur. As a result, small children develop shrill crying, which can also cause psychological discomfort to parents and relatives. If treatment is not received, mental disorders usually occur in the child as well. For this reason, an early therapy of this disease is necessary to prevent consequential damages. The symptoms can be alleviated with the help of medication or diet, so that the child’s development can progress in a normal manner. In this process, the child’s life expectancy is not reduced.
Prevention
Because maple syrup disease is genetic, it cannot be prevented. Chromosomal analysis can be performed prenatally to determine the enzyme defect in the amniotic cells (amniotic fluid cells). In addition, people affected by maple syrup disease should follow the protein-restricted diet and learn to avoid possible triggering factors such as stress.
Follow-up
Maple syrup disease conditions a genetic condition that is present from childhood. However, with appropriate treatment, patients can lead a largely normal life. In contrast, a causal cure is impossible. Planned aftercare represents a combination of medical support and self-responsible action. In order to prevent developmental disorders, early initiation of treatment is essential. In newborns, the disease is detected in screening programs. Medical follow-up is much more frequent until the growth phase than in adulthood. Doctors check blood and urine levels. Beyond that, the patient’s own responsibility takes effect. Whereas in younger years the parents still bore the responsibility for a lifelong diet, this responsibility passes to the patient himself as he grows older. Low-protein products are to be consumed. Dietary supplements represent an integral part of life. The daily routine should also be aimed at preventing complications. Stress as a psychosomatic component also unfolds effects on the physique. Sometimes it is therefore advisable to cut back on work. Liver transplantation is indicated in extreme cases and in combination with other diseases.
What you can do yourself
In the case of maple syrup disease, there are no self-help methods that could act on the causes of the disease. This is due to the fact that it is a genetic condition. Instead, self-help options are closely tied to treatment recommendations. Especially in the first years of life, when awareness of the need for an adapted diet may not be sufficient, parents and relatives have a particular responsibility.You need to keep an eye on the diet and health of the person with the disease. This may include increased precautions that are taken. Coupled with the fact that infections and surgery can lead to serious complications (cerebral edema, ketoacidosis) in people with maple syrup disease, maintaining the health of the sufferer is important for a good prognosis. Accordingly, affected individuals are well advised to take care of themselves throughout their lives. Risks of illness and accidents should be avoided as much as possible. The diet must remain consistent. This is often accompanied by a diet that is not very varied and is completed by protein supplements. Since leucinosis, insofar as it is not a lethal form, does not otherwise entail any restrictions, affected persons can lead a largely normal life. If a few dietary rules are observed, even visits to restaurants can be quite successful.
