Methylmalonic Acidemia (MMA)
Description
Methylmalonic acidemia (MMA), also known as methylmalonyl CoA mutase deficiency, is a rare inherited metabolic disorder. It prevents the body from properly breaking down certain proteins and fats. This breakdown process produces a substance called methylmalonic acid, which builds up in the blood and urine, leading to various health complications. This article delves into the intricacies of MMA, explaining its causes, signs, diagnosis, management strategies, and how individuals with MMA can lead fulfilling lives.
Genes Involved
MMA is caused by mutations in one of several genes involved in the metabolic pathway for breaking down certain proteins and fats. These genes include:
- MUT: This gene provides instructions for producing the enzyme methylmalonyl CoA mutase, which is essential for breaking down methylmalonic acid.
- MMACHC: This gene codes for a protein that helps the MUT enzyme function correctly.
- MMADHC: This gene provides instructions for creating an enzyme required for the synthesis of vitamin B12.
- MMAA: This gene codes for a protein that helps attach vitamin B12 to the MUT enzyme.
Recognizing the Signs and Symptoms
MMA symptoms can vary in severity and often appear shortly after birth. Common signs include:
- Failure to thrive: Difficulty gaining weight or slow growth.
- Vomiting and diarrhea: Frequent episodes of vomiting and loose stools.
- Lethargy and weakness: Feeling tired and lacking energy.
- Acidosis: A buildup of acid in the blood, leading to rapid breathing and a fruity odor on breath.
- Seizures: Sudden and uncontrolled electrical activity in the brain.
- Developmental delays: Slowed development in motor skills, language, and cognition.
- Encephalopathy: Brain dysfunction causing confusion, disorientation, and coma.
- Metabolic acidosis: A buildup of acid in the blood, causing breathing difficulties and a fruity odor on breath.
- Kidney problems: Damage to the kidneys, leading to difficulty filtering waste.
- Heart problems: Cardiomyopathy, which is a weakening of the heart muscle.
- Anemia: Low red blood cell count, causing fatigue and weakness.
- Pancreatitis: Inflammation of the pancreas, leading to abdominal pain and digestive issues.
Causes
MMA is caused by a genetic mutation that prevents the body from breaking down certain proteins and fats effectively. This leads to an accumulation of methylmalonic acid in the blood and urine. The mutations can occur in any of several genes involved in the breakdown process.
Inheritance/recurrence risk
MMA is typically inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to inherit the disorder. If both parents are carriers, there is a 25% chance that their child will inherit MMA, a 50% chance of being a carrier, and a 25% chance of not inheriting the mutation. Genetic testing is available to determine if a person carries the mutated gene.
