Methylmalonic aciduria is a metabolic disease. The disease may also be synonymously referred to as methylmalonic acidemia or with the abbreviation MMA. It is usually extremely rare, so only a relatively small number of people have the disorder. The disease is usually classified under the category of organoacidopathies. Methylmalonic aciduria is primarily inherited in an autosomal recessive manner.
What is methylmalonic aciduria?
Basically, methylmalonic aciduria is characterized by an unusually high accumulation of methylmalonic acid, which is then excreted from the body via the kidneys. The frequency of the disease is around 1 in 50,000, making it a very rare inherited disorder. See AbbreviationFinder for abbreviations related to MMA.
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. This gradually builds up the substance methylmalonyl-CoA.
In this way, so-called intoxications develop, which lead to metabolic crises. If these crises do not receive adequate therapy, they may be accompanied by brain lesions within a short period of time. In some cases, they also lead to the death of the person concerned relatively quickly.
On the one hand there is the hereditary form of methylmalonic aciduria, on the other hand there is also an diet-related type of the disease. This primarily develops when there is a severe lack of vitamin B12.
A characteristic mechanism is present in the development of methylmalonic aciduria, which over time leads to the manifestation of the disease. In the majority of cases, a disruption in the breakdown of the substance methylmalonyl-CoA is decisive for the development of the disease. This substance is formed from the so-called propionyl-CoA, which results from the breakdown of special amino and fatty acids.
In this case, possible amino acids are, for example, methionine and isoleucine. In physiological states, the substance succinyl-CoA develops from the methylmalonyl-CoA, which subsequently becomes a component of the citric acid cycle. However, the corresponding conversion step is impaired in the context of methylmalonic aciduria, since a special enzyme does not work properly here.
Medical research primarily knows three genes in which corresponding mutations occur that ultimately lead to the development of methylmalonic aciduria. First, it is MCM, which is responsible for encoding methylmalonyl-CoA mutase. If the responsible enzyme is missing as a result of various mutations, the normal process is disrupted.
If the methylmalonic aciduria is due to such mutations, the administration of vitamin B12 usually does not alleviate the symptoms. If MMAA or MMAB are prominent, other disorders develop. Because these are responsible for coding enzymes that play a role in the formation of the substance adenosylcobalamin.
The focus here is on the cobalamin derivative. Another case is when methylmalonic aciduria develops without genetic components. This is usually a serious lack of vitamin B12, which leads to the development of the typical symptoms.
Symptoms, Ailments & Signs
Methylmalonic aciduria is characterized by certain complaints and symptoms that are similar in all patients. Nevertheless, individual deviations in the clinical appearance of the disease are possible. Certain symptoms dominate in some people, while other symptoms are more prevalent in other patients.
Basically, methylmalonic aciduria is characterized by intoxication, in which the urea cycle and gluconeogenesis are consecutively impaired. This results in the typical symptoms of the disease, namely hyperammonemia, metabolic encephalopathy and a ketoacidotic state of the metabolism.
Potential long-term damage from methylmalonic aciduria may build up in the kidney. This is because so-called tubulointerstitial nephritis develops in some patients due to the permanently high elimination of methylmalonic acid via the kidneys. In some cases, this develops into chronic kidney failure.
Diagnosis & disease progression
The diagnosis of methylmalonic aciduria can be made in a number of ways and usually involves different methods. First of all, the discussion with the patient plays an important role. The doctor discusses the present complaints as well as past illnesses of the person concerned. Personal lifestyle is also discussed.
This is followed by clinical examinations. For example, a so-called blood gas analysis is carried out. Certain organic acids and other substances are also examined. With regard to the differential diagnosis, other types of organoacidopathies are particularly important.
Due to methylmalonic aciduria, those affected 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 those affected to also suffer from methylmalonic aciduria, which significantly reduces their quality of life.
In addition, most sufferers will develop kidney damage if the disease is not treated. In the worst case, renal insufficiency can also occur, which if left untreated can lead to the death of the patient. Those affected are then usually dependent on dialysis or a donor kidney.
However, there are no further complications or special symptoms with methylmalonic aciduria. Most of the limitations and symptoms of this disease can be treated relatively well with a special diet. In most cases, there are no complications.
However, those affected are usually dependent on this diet and supplements their entire lives, since a causal treatment of this disease is not possible. It cannot generally be predicted whether this will lead to a reduction in life expectancy.
When should you go to the doctor?
If irregularities in the metabolism are noticed, a doctor should be consulted for an intensive check-up. If there are diffuse symptoms that the person concerned cannot explain, a visit to a doctor is recommended. If there is a decrease in general performance, a feeling of illness or a decrease in the usual physical activities, a visit to the doctor is advisable. A doctor is required in the event of problems with kidney activity or peculiarities when going to the toilet. A changed amount of urine, changes in smell or pain are signs of an existing health impairment. A feeling of inflammation in the organism as well as a restriction of kidney function must be examined and treated by a doctor.
If, despite a healthy lifestyle and a balanced diet, a steady drop in the available energy reserves is observed, there is cause for concern. If the usual everyday duties can no longer be carried out, if you become exhausted quickly or if your susceptibility to infections increases, then there is a disorder. A doctor should be consulted so that a diagnosis can be made. If the person affected suffers from mood swings, increased irritability or inner restlessness, a doctor should be consulted. Nerve problems, sensory disturbances on the skin, muscle weakness and problems maintaining concentration are indications of an existing disease. They have to be checked out by a doctor.
Treatment & Therapy
Various options are available for the treatment of methylmalonic aciduria. As a rule, the affected patients are prescribed a diet that contains only a very small proportion of proteins. This diet is usually maintained throughout life. In addition, it may be advisable to substitute the substance L-carnitine. If methylmalonic aciduria is a consequence of the disturbance in the metabolism of cobalamin, vitamin B12 should be taken as a supplement.
Outlook & Forecast
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 the symptoms at any time if the guidelines discussed are not adhered to. The therapy of methylmalonic aciduria is almost exclusively aimed at changing the daily diet. For this reason, the affected person does not require any medical or drug treatment. Only the change in everyday life leads to freedom from symptoms. In order to alleviate the symptoms and thus improve general health, the complete intake of food must be adapted to the individual needs of the organism.
In most cases, a special diet containing a very small amount of protein is recommended. If the person concerned adheres to the doctor’s instructions, there will be a continuous change in the organism. However, the change in food intake must be long-term and take place over the entire lifespan. Otherwise, a recurrence of the complaints is to be expected. Even sporadic optimizations are not sufficient. In addition, a protein-rich diet can damage the internal organs. The kidneys in particular are attacked in these cases. In the event of an unfavorable course of the disease, the person concerned is threatened with chronic kidney weakness and consequently an unfavorable prognosis.
Since methylmalonic aciduria is usually an inherited metabolic disease, no effective ways of preventing the disease have been researched.
You can do that yourself
As a rule, methylmalonic aciduria can be treated relatively well by means of self-help. Medical treatment is not always necessary. However, regular medical examinations are always advisable in the case of a chronic illness, since methylmalonic aciduria cannot be completely curtailed.
The symptoms and symptoms of the disease are mainly limited by a special diet. This diet should be low in protein, and no restrictions are necessary. However, this means that the affected person should avoid eggs or milk in his everyday life if possible. Meat should also only be eaten in small amounts in order not to aggravate the symptoms. Taking L-carnitine can often also have a positive effect on the course of the disease, so patients should ensure that they take it regularly. Vitamin B12 can also be taken if cobalamin is responsible for the metabolic disorder and thus for the methylmalonic aciduria.
Contact with other people affected by methylmalonic aciduria is also helpful, as this can lead to the exchange of information or prescriptions, which improves the quality of life.