Methylmalonic aciduria
| Methylmalonic acidemia | |
|---|---|
 |
|
| Methylmalonic acid | |
| Classification and external resources | |
| Specialty | endocrinology |
| ICD-10 | E71.1 |
| ICD-9-CM | 270.3 |
| OMIM | 251000 251100 251110 277380 277400 277410 606169 |
| DiseasesDB | 29509 29510 |
| MedlinePlus | 001162 |
| eMedicine | neuro/576 |
Methylmalonic acidemia (MMA), also called methylmalonic aciduria, is an autosomal recessivemetabolic disorder. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.
Methylmalonic acidemia stems from several genotypes, all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated. It is estimated that this disorder has a frequency of 1 in 48,000 births, though the high mortality rate in diagnosed cases make exact determination difficult. Methylmalonic acidemias are found with an equal frequency across ethnic boundaries.
Depending on the affected gene(s), this disorder may present symptoms that range from mild to life-threatening.
The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.
Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia.
This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene—one from each parent—must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.
Though not always grouped together with the inherited versions, a severe nutritional deficiency of vitamin B12 can also result in syndrome with identical symptoms and treatments as the genetic methylmalonic acidemias. Methylmalonyl CoA requires vitamin B12 to form succinyl-CoA. When the amount of B12 is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B12 deficiency in serum.
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Wikipedia