MACD stands for Medium-chain acyl-CoA dehydrogenase deficiency. Medium-chain acyl-CoA dehydrogenase deficiency ( MACD deficiency ) is a genetic metabolic disorder in which medium-chain fatty acids are not sufficiently broken down. Under certain conditions, dangerous metabolic imbalances can occur, which can sometimes be fatal. If treatment is started early, the disease can be easily controlled.
What is Medium Chain Acyl-CoA Dehydrogenase Deficiency?
In medium-chain acyl-CoA dehydrogenase deficiency, the breakdown of medium-chain fatty acids is disrupted due to genetic causes. These can no longer be sufficiently used to generate energy. Therefore, the body is forced to break down carbohydrates and amino acids to an increased extent. See AbbreviationFinder for abbreviations related to MACD.
If the energy requirement increases due to increased physical exertion, growth processes or infections, the body’s carbohydrate reserves and endogenous proteins are increasingly used to generate energy. The same applies to long-term food abstinence. Under these conditions, fatty acid degradation is normally promoted by beta-oxidation.
However, this is not sufficiently possible with a MACD deficiency. The resulting increased breakdown of glucose leads to dangerous hypoglycaemia. Due to the forced breakdown of amino acids, the ammonia content in the blood increases at the same time. Carnitine, which is important for energy metabolism, is reduced because it forms compounds with the accumulating medium-chain fatty acids.
The compounds represent intermediate products of fatty acid degradation. Since further degradation of the medium-chain fatty acids is blocked by a defective enzyme in the acyl-hydrogenase complex, a secondary carnitine deficiency develops. A strong deviation from the corresponding values can lead to life-threatening complications. If left untreated, about 25 percent of the metabolic imbalances caused by this disorder are fatal.
Overall, medium-chain acyl-CoA dehydrogenase deficiency is one of the most common metabolic diseases and is part of the examinations as part of newborn screening. Timely determination of the responsible gene defect is necessary for effective therapy. This disease is easily treatable with appropriate therapy measures.
Causes
The cause of the medium-chain acyl-CoA dehydrogenase deficiency is to be found in a malfunction of the MCAD enzyme. Due to an autosomal recessive mutation of the MCAD gene, which is located on chromosome 1, the folding properties of the enzyme are impaired. A misfolded enzyme occurs, which is eliminated and degraded as part of a protein quality control.
As a result, there is too little medium-chain acyl-CoA dehydrogenase. Medium-chain fatty acids are then only broken down insufficiently. As already mentioned, an autosomal recessive mutation of the MCAD gene is responsible for this disease. In the case of autosomal recessive inheritance, the affected patient has two defective genes, one copy each of which was transferred from both parents.
Individuals with only one mutated gene do not become ill. Therefore, the disease is not inherited from generation to generation. If both parents are heterozygous for one defective gene, the offspring have a 25 percent chance of developing MCAD deficiency.
Symptoms, Ailments & Signs
Medium-chain acyl-CoA dehydrogenase deficiency is characterized by a predisposition to hypoglycemia, convulsions, and comatose states. The first symptoms usually appear between the ages of two months and four years. They are triggered by infections or prolonged abstinence from food and manifest themselves as diarrhea, vomiting, disturbances of consciousness and seizures.
The liver may be enlarged. With every metabolic imbalance, the blood sugar levels are reduced, the ammonia levels in the blood are increased and the carnitine level is reduced. The greater the deviations, the greater the risk of falling into a life-threatening coma. However, there are also forms of MCAD deficiency with much milder symptoms.
In some cases, there are no symptoms at all. Here only laboratory tests point to a corresponding genetic defect. Even in the more severely ill patients, there are always symptom-free phases between the metabolic imbalances.
Diagnosis & disease progression
Medium-chain acyl-CoA dehydrogenase deficiency can be detected during newborn screening using tandem mass spectroscopy. With this method, fragments of acyl carnitines are determined. The concentration of octanoylcarnitine is the key parameter here. If levels are elevated, DNA testing can help confirm the diagnosis.
In the acute phase of the disease, hypoglycaemia, increased levels of ammonia and increased levels of medium-chain fatty acids in the form of dicarboxylic acids can be detected in the urine. There is also hyperuricemia (elevated levels of uric acid in the urine) and signs of liver dysfunction. Sometimes the myoglobin levels in the urine are also increased.
Complications
In the worst case, the medium-chain acyl-CoA dehydrogenase deficiency can be fatal for the patient. In order to avoid serious complications and consequential damage, this disease must be treated at an early stage. In most cases, those affected suffer from severe cramps, which are also associated with pain.
Likewise, the medium-chain acyl-CoA dehydrogenase deficiency can lead to a coma or loss of consciousness, so that the everyday life of the person affected is significantly restricted by the complaint. Consciousness disorders occur and those affected suffer from diarrhea and vomiting. In many cases, there is also an enlargement of the liver, which is also associated with pain.
If the person concerned is in a coma, this condition can also have a negative effect on the psyche of the relatives or the parents and children and lead to depression or other mental upsets in these people. As a rule, medium-chain acyl-CoA dehydrogenase deficiency can be treated relatively well if it is diagnosed early.
There are no particular complications. Only with a late diagnosis and treatment can various complications arise, so that the person concerned is dependent on an operation, for example.
When should you go to the doctor?
Food cravings and associated symptoms such as nausea and vomiting are signs of health problems. If there are problems with concentration, a feeling of discomfort or a decrease in the level of performance, a doctor is needed. In the case of pain, cramps and a seizure disorder, a doctor should be consulted immediately. Listlessness, loss of appetite or an increased susceptibility to infections must be examined and treated. Since the disease shows the first symptoms between the ages of six months and four years of age, small children in particular are at risk of developing the disease. If those affected show a noticeable change in their weight, listlessness or behavioral problems, a doctor should be consulted.
In the case of disorders of consciousness, increased vigilance is necessary. Since the risk of an accident or injury increases due to the reduced awareness of the person concerned, there is a need for action. If a comatose state occurs or if there is a loss of consciousness, an emergency service should be alerted. At the same time, first aid measures are required until it arrives. Swelling of the upper body, tiredness, exhaustion as well as inner restlessness and increased irritability should be presented to a doctor. The disease is characterized by a phased regression of all symptoms. Despite the symptom-free period, a doctor’s visit is advisable as soon as signs of health impairment appear repeatedly.
Treatment & Therapy
If the diagnosis is made early, the prognosis of the disease is very good. Then prophylactic measures can be initiated in good time to prevent metabolic crises even in difficult and stressful situations. It is important to avoid long periods of fasting and infections.
Fasting should not last longer than two hours. Knowledge of this disease is also necessary for the preparation of possible operations. Many operations that are not absolutely necessary should therefore not be carried out. If an operation cannot be avoided, artificial nutrition with glucose solution is absolutely necessary to prevent metabolic imbalance.
Even an acute metabolic imbalance can only be overcome by an infusion of glucose solution. Since carnitine is missing, oral administration of carnitine is also useful. Furthermore, the administration of riboflavin can lead to an improvement in lipid metabolism because it is a coenzyme in the breakdown of fatty acids.
Outlook & Forecast
If there is a medium-chain acyl-CoA dehydrogenase deficiency, the prognosis is positive if the diagnosis is made as early as possible. However, under certain conditions, this congenital metabolic defect can lead to serious metabolic imbalances and death.
The problem is that a medium-chain acyl-CoA dehydrogenase deficiency is variable in the clinical picture. Therefore, misdiagnosis cannot be ruled out. The symptoms of medium-chain acyl-CoA dehydrogenase deficiency are already noticeable in newborns. In order to improve the prospects for those affected, metabolic screening is usually carried out on newborns.
Living conditions are good as long as the sufferer avoids prolonged periods of sobriety or starvation. He should maintain a low-fat diet that contains sufficient amounts of carbohydrates. In addition, a carnitine deficiency must be taken care of. In order to prevent an imminent metabolic imbalance, the administration of glucose-electrolyte infusions can also be considered.
Emergencies and impending metabolic imbalances represent a high risk. Therefore, those affected by medium-chain acyl-CoA dehydrogenase deficiency should be taken to hospital immediately if necessary. MCAD sufferers carry an emergency ID card identifying them as having medium-chain acyl-CoA dehydrogenase deficiency.
The outlook is worse for people with medium-chain acyl-CoA dehydrogenase deficiency if they catch infections or are fasting. Being sober before an operation also entails major risks. Metabolic disorders can lead to hypoketotic hypoglycemia or metabolic acidosis. Unconsciousness or death can occur if neurological symptoms such as hypotension or lethargy occur.
Prevention
Because medium-chain acyl-CoA dehydrogenase deficiency is genetic, there is no recommendation for its prevention. In the case of familial accumulation, human genetic counseling makes sense if there is a desire to have children. The defective genes can be detected by DNA tests.
If both parents each have a mutated gene, the offspring has a 25 percent risk of developing medium-chain acyl-CoA dehydrogenase deficiency. If MCAD deficiency is detected during newborn screening, comprehensive medical control is necessary to prevent infections. The diet must be adjusted to a high-carbohydrate and low-fat diet.
Aftercare
Since the peroxisomal disease is based on a genetic defect, therapy can only alleviate a few symptoms without being able to completely cure the disease. For this reason, there is no actual aftercare treatment in this sense, but intensive symptom treatment to alleviate some suffering.
In general, those affected and their families are advised to lead a healthy lifestyle with a balanced diet to support the immune system. He will also suggest certain relaxation and mental techniques for stabilization and advise as many leisure activities as possible. Mental balance makes it easier to deal with the disease and can sometimes promote recovery. If the parents who have already been affected wish to have another child, a precise genetic test is recommended to determine in advance the probability of having another child with the disease.
You can do that yourself
Medium-chain acyl-CoA dehydrogenase deficiency is a metabolic disease that can be treated effectively if caught early. An important self-help measure is to regulate the metabolism through diet and sufficient exercise. People who regularly take medication or engage in activities that negatively affect their metabolism should speak to their family doctor. With appropriate therapy, the metabolism can be optimized and thus MCADD can also be treated well.
In addition to medical treatment, alternative therapy is also possible. Natural remedies such as valerian or sage can have a positive impact on the healing process due to their pain-relieving effect and other positive effects. In order to minimize any risks and side effects, the use of appropriate preparations should first be discussed with the responsible doctor.
Parents whose child has died from MCADD should seek trauma therapy. If you become pregnant again, screening should be carried out at an early stage so that a possible medium-chain acyl-CoA dehydrogenase deficiency can be detected and sudden infant death syndrome can be averted. The affected children require constant observation so that the medical emergency service or the rescue service can be contacted immediately in the event of any complications.