Methylmalonic aciduria is a disease of the metabolism. The disease may also be referred to synonymously as methylmalonacidemia or by the abbreviation MMA. It is generally exceedingly rare, so only a relatively small number of people have the disorder. The disorder is usually included in the category of organoacidopathies. Methylmalonic aciduria is inherited primarily in an autosomal recessive manner.
What is methylmalonic aciduria?
Basically, methylmalonic aciduria is characterized by the accumulation of an abnormally high amount of methylmalonic acid, which is subsequently excreted from the body by the renal route. The frequency of the disease is about 1:50,000, so it is a very rare inherited disorder. In principle, there is a defect in a specific enzyme that depends on vitamin B12. As a result, the breakdown of specific amino and fatty acids is disturbed. These are primarily the substances isoleucine, valine, threonine, methionine and cholic acid. Thus, an accumulation of the substance methylmalonyl-CoA gradually develops. In this way, so-called intoxications are formed, which lead to crisis states in the metabolism. If these crises do not receive adequate therapy, they may be accompanied by lesions of the brain in short periods of time. In some cases, they also lead relatively quickly to the death of the affected person. On the one hand, there is a hereditary form of methylmalonic aciduria, on the other hand, there is also an alimentary type of the disease. This forms primarily when there is a severe deficiency of vitamin B12.
Causes
In the development of methylmalonic aciduria, there is a characteristic mechanism that leads to the manifestation of the disease over time. The decisive factor for the development of the disease in the majority of cases is a disturbance in the degradation of the substance methylmalonyl-CoA. This substance is formed from the so-called propionyl-CoA, which is produced in the course of the degradation of special amino and fatty acids. Possible animoacids in this case are, for example, methionine and isoleucine. In physiological conditions, the substance succinyl-CoA develops from the methylmalonyl-CoA, which subsequently becomes a component of the citrate cycle. However, the corresponding conversion step is impaired in the context of methylmalonaziduria, since a special enzyme does not work and act properly here. Medical research is primarily aware of three genes in which corresponding mutations occur that ultimately lead to the development of methylmalonic aciduria. First is MCM, which is responsible for coding methylmalonyl-CoA mutase. In the absence of the responsible enzyme due to various mutations, the usual process is disturbed. If methylmalonaciduria is due to such mutations, the administration of vitamin B12 does not usually provide relief from the symptoms. If MMAA or MMAB are in the foreground, other disorders develop. This is because these are responsible for the coding of enzymes that play a role in the formation of the substance adenosylcobalamin. In particular, this involves the cobalamin derivative. Another case is when methylmalonic aciduria occurs without genetic components. This usually involves a severe deficiency of vitamin B12 that leads to the expression of the typical symptoms.
Symptoms, complaints, and signs
Methylmalonic aciduria is characterized by certain complaints and symptoms that are similar in all patients. Nevertheless, individual variations in the clinical presentation of the disease are possible. Thus, certain symptoms dominate in some individuals, while other complaints are more prevalent in other patients. Basically, methylmalonic aciduria is characterized by intoxication in which the cycle of urea as well as gluconeogenesis are consecutively impaired. This results in the typical symptoms of the disease, namely hyperammonemia, metabolic encephalopathy, and a ketoacidotic state of metabolism. Potential long-term damage from methylmalonic aciduria may form on the kidney. This is because due to the permanently high elimination of methylmalonic acid via the kidneys, a so-called tubulointerstitial nephritis forms in some patients. In some cases, chronic kidney weakness develops from this.
Diagnosis and course of the disease
The diagnosis of methylmalonic aciduria can be made in several ways and usually involves different methods. First, the patient interview plays an important role. The physician discusses the present complaints as well as past illnesses of the affected person. Personal lifestyle is also discussed. This is followed by clinical examinations. For example, a so-called blood gas analysis is performed. Certain organic acids and other substances are also examined. In terms of differential diagnosis, other types of organoacidopathies are particularly significant.
Complications
Because of methylmalonic aciduria, affected individuals primarily suffer from a metabolic disorder. This can have very different effects, so that a general course of this disease cannot usually be predicted. It is not uncommon for sufferers of methylmalonic aciduria to also suffer from psychological complaints that significantly reduce their quality of life. Furthermore, damage to the kidneys occurs in most sufferers if the disease is not treated. In the worst case, renal insufficiency also occurs, which can lead to the death of the patient if left untreated. Those affected are then usually dependent on dialysis or a donor kidney. However, no other complications or special complaints occur in methylmalonic aciduria. Most of the limitations and complaints of this disease can be treated relatively well by a special diet. This also does not result in complications in most cases. However, affected individuals are usually dependent on this diet and supplements for the rest of their lives, as causal treatment of this disease is not possible. Whether this will result in a reduction in life expectancy cannot generally be predicted.
When should you see a doctor?
If metabolic irregularities are noticed, a physician should be consulted for an intensive checkup. If diffuse complaints occur that the affected person cannot explain, a visit to a physician is recommended. If there is a decrease in general performance, a feeling of illness or a decline in the usual physical activities, a visit to the doctor is advisable. If there are complaints of kidney activity or peculiarities in going to the toilet, a doctor is needed. An altered urine volume, changes in odor or pain are signs of an existing health impairment. A feeling of inflammation in the organism as well as a restriction of kidney function should be examined and treated by a doctor. If, despite a healthy lifestyle and a balanced diet, a steady decline in available energy reserves is observed, there is cause for concern. If the usual daily tasks can no longer be performed, rapid exhaustion occurs or susceptibility to infections increases, a disorder is present. A physician should be consulted so that a diagnosis can be made. If the affected person suffers from mood swings, increased irritability or inner restlessness, a doctor should be consulted. Complaints of the nerves, sensory disturbances on the skin, muscle weakness and problems in maintaining concentration are indications of a present disease. They should be evaluated by a physician.
Treatment and therapy
Various options are available for the treatment of methylmalonic aciduria. Usually, affected patients are prescribed a diet that contains only a very small amount of proteins. This diet is usually to be maintained throughout life. In addition, it may be advisable to substitute the substance L-carnitine. If methylmalonic aciduria is a consequence of the disturbance of the metabolism of cobalamin, vitamin B12 should be taken as a supplement.
Outlook and prognosis
In this disease, the prognosis is usually favorable if the patient cooperates. Nevertheless, it is a chronic disease that can lead to a recurrence of symptoms at any time if discussed guidelines are not followed. The therapy of methylmalonic aciduria is almost exclusively focused on a change in the daily diet. For this reason, the affected person does not need any medical or drug treatment. Only the change in everyday life leads to freedom from symptoms.To alleviate the symptoms and thus improve overall health, the complete intake of food should be adapted to the individual needs of the organism. In most cases, a special diet is recommended, which contains a very small amount of proteins. Provided that the person concerned adheres to the doctor’s instructions, there is a continuous change in the organism. However, the change in food intake must be long term and throughout the life span. Otherwise, a relapse of the complaints is to be expected. Even sporadic optimizations are not sufficient. In addition, a protein-rich diet can cause damage to the internal organs. In particular, the kidney is attacked in these cases. Thus, the affected person is threatened with an unfavorable course of the disease of chronic kidney weakness and consequently an unfavorable prognosis.
Prevention
Because methylmalonic aciduria is mostly a congenital metabolic disorder, no effective ways to prevent the disease have been explored.
Here’s what you can do yourself
In general, methylmalonic aciduria can be treated relatively well by self-help means. Medical treatment is not necessary in every case. However, regular medical checkups are always advisable for a chronic disease, as methylmalonic aciduria cannot be completely controlled. The symptoms and complaints of the disease are mainly limited by a special diet. This diet should be low in proteins, furthermore no restrictions are necessary. This means, however, that the affected person should avoid eggs or milk in his daily life as much as possible. Eating meat should also be done only in small quantities so as not to increase the symptoms. Frequently, the intake of L-carnitine can also have a good effect on the course of the disease, so that patients should make sure that they take it regularly. Vitamin B12 can be taken additionally if cobalamin is responsible for the metabolic disorder and thus for methylmalonic aciduria. Likewise, contact with other sufferers of methylmalonaciduria is helpful, as this can lead to the exchange of information or prescriptions, through which the quality of life is increased.
