Methylmalonic Acidemia: Diagnosis And Treatment
Methylmalonic acidemia is a congenital anomaly affecting the metabolism of vitamin B12. The body cannot break down certain proteins and fats, resulting in an accumulation of methylmalonic acid in the blood.
The disease is usually diagnosed in the first year of life. About 1 in 25,000 / 48,000 newborns is born with this disease. Symptoms are evident in childhood and vary from case to case.
Causes of methylmalonic acidemia
The cause of vitamin B12-sensitive methylmalonic acidemia is a defect in the synthesis of the adenosyl-cobalamin cofactor (AdoCbl), caused by genetic alterations of the MMAA (4q31.1-2), MMAB (12q24.1) and MMADHC (2q23) genes. 2).
Vitamin B12-resistant methylmalonic acidemia is due to a total or partial deficiency in the activity of the mitochondrial enzyme methylmalonyl-Coa mutase. However, in this case the mutations concern the MUT gene (6p21).
Nevertheless, all forms of methylmalonic acidemia are transmitted according to an autosomal recessive pattern of inheritance.
Symptoms
The signs and symptoms of methylmalonic acidemia can be vomiting, dehydration, hypotonic, developmental delay, fatigue, and hepatomegaly. On the other hand, in the long run, complications can arise, among which we find:
- Digestive disorders.
- Cognitive disability.
- Chronic kidney disease.
- Pancreatitis or inflammation of the pancreas.
If the patient does not receive adequate treatment, he can go into a coma or even die. Individuals with isolated methylmalonic acidemia may have the following symptoms, depending on the form in which the disease occurs:
Infant form
It is the vitamin B12-resistant enzyme subtype and is the most common form of isolated methylmalonic acidemia. It occurs in childhood. Babies appear to be fine at birth, however, they soon exhibit symptoms such as lethargy, vomiting, and dehydration.
Later, liver enlargement becomes evident, as well as hypotonia and encephalopathy. As for laboratory analyzes, the following parameters are measured:
- Ketonuria and ketosis.
- Ammonia in the blood.
- Severe metabolic acidosis.
- Increased blood glycine.
Partial deficit form
It is the form sensitive to vitamin B12 and occurs in the first months or years of life. Affected children may have eating disorders, such as anorexia, vomiting, hypotonia and developmental delay.
In some cases, following the ingestion of proteins, there may be episodes of vomiting. Children affected by this form of methylmalonic acidemia are at risk of metabolic decompensation, so diagnosis is very important, as is the timely initiation of therapy.
In general, until the first episode of vomiting, dehydration, lethargy or coma occurs, it is not possible to know if the subject suffers from this metabolic alteration.
Benign form or adult form
Those affected by this disease are considered stable but vulnerable to acute metabolic decompensation. The cause of this form of methylmalonic acidemia has not been fully understood.
Treatment of methylmalonic acidemia
Treatment should be initiated promptly once the diagnosis is made. The sooner you start, the better the patient’s response will be.
Diet is the basis of treatment for methylmalonic acidemia today. Food treatment aims to prevent the accumulation of substrates and metabolites associated with toxic levels.
Treatments recommended for children with methylmalonic acidemia are:
- L-carnitine: this substance, in addition to being safe and natural, helps the body to produce energy and eliminate toxins.
- Oral antibiotics: These drugs help reduce the amount of methylmalonic acid in the intestine.
- Vitamin B12 injections: Over 90% of CblA deficient cases respond to this treatment. In addition, it helps about 40% of children with CblB deficiency.
In case there are symptoms of a metabolic crisis, you need to go to the hospital. Hospital treatment involves venous bicarbonate in order to lower the acidity of the blood.
In addition, glucose is often given intravenously to prevent the breakdown of protein and fat stored in the body.
Prevention of methylmalonic acidemia
A diet low in amino acids and with limited amounts of protein is recommended. The diet will consist mainly of carbohydrates, such as cereals, fruit, pasta and vegetables.
People with this disease should avoid contact with people with infectious diseases, such as colds or flu, in order to avoid complications.
