Summary about Disease
Methylmalonic acidemia (MMA) due to methylmalonyl-CoA mutase deficiency is a metabolic disorder where the body cannot properly break down certain proteins and fats. This leads to a buildup of methylmalonic acid and other harmful substances in the blood and urine, affecting organs and tissues. It is classified as a type of organic acidemia.
Symptoms
Symptoms vary depending on the severity of the deficiency and the specific type of MMA. Common symptoms include:
Poor feeding
Vomiting
Lethargy
Failure to thrive
Developmental delays
Intellectual disability
Seizures
Muscle weakness (hypotonia)
Enlarged liver (hepatomegaly)
Kidney problems
Coma Some individuals may have milder, late-onset forms with symptoms appearing later in childhood or adulthood, often triggered by illness or stress.
Causes
MMA due to methylmalonyl-CoA mutase deficiency is caused by mutations in the MUT gene. This gene provides instructions for making the methylmalonyl-CoA mutase enzyme. This enzyme is essential for converting methylmalonyl-CoA into succinyl-CoA, a crucial step in the breakdown of certain amino acids and fats. A mutation in MUT gene results in a non-functional or deficienct methylmalonyl-CoA mutase enzyme, leading to the accumulation of methylmalonic acid. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Treatment focuses on managing symptoms and preventing complications. Medications used may include:
Vitamin B12 (Cobalamin): Some individuals respond to high doses of B12, which can help improve enzyme function.
L-Carnitine: Helps remove accumulated organic acids.
Antibiotics: To reduce the production of propionic acid by gut bacteria.
Sodium Benzoate/Phenylbutyrate: Assists in removing waste products. Alongside medication, dietary management is very important.
Is Communicable
No, MMA due to methylmalonyl-CoA mutase deficiency is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.
Precautions
Precautions focus on managing the condition to prevent metabolic crises. These include:
Strict dietary management: This involves restricting the intake of protein, particularly the amino acids isoleucine, valine, threonine, and methionine.
Regular monitoring: Monitoring blood and urine levels of methylmalonic acid and other metabolites is crucial.
Prompt treatment of illness: Any illness, infection, or stress can trigger a metabolic crisis and requires immediate medical attention.
Emergency plan: Families should have a written emergency plan outlining what to do in case of a metabolic crisis.
Avoid prolonged fasting.
How long does an outbreak last?
MMA isn't characterized by outbreaks. However, metabolic crises can occur. The duration of a metabolic crisis depends on the severity, promptness of treatment, and individual response. A mild crisis, treated early, might resolve in a few days. A severe crisis can last longer and may require hospitalization for several weeks.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many states include MMA in their newborn screening programs. Elevated levels of propionylcarnitine (C3) in blood spots may indicate MMA.
Urine organic acid analysis: This test measures the levels of organic acids in the urine, including methylmalonic acid.
Blood amino acid analysis: This test measures the levels of amino acids in the blood.
Genetic testing: Genetic testing can confirm the diagnosis by identifying mutations in the MUT gene.
Enzyme assay: An enzyme assay measuring methylmalonyl-CoA mutase activity in cultured fibroblasts can confirm the diagnosis.
Timeline of Symptoms
The timeline of symptoms varies depending on the severity of the deficiency:
Severe, Early-Onset Forms: Symptoms can appear within days or weeks of birth.
Late-Onset Forms: Symptoms may not appear until later in childhood or adulthood, often triggered by illness, stress, or increased protein intake. These individuals may experience recurrent episodes of metabolic decompensation.
Important Considerations
Early diagnosis and treatment are crucial to prevent severe complications and improve long-term outcomes.
Lifelong management is required, including dietary restrictions, medication, and regular monitoring.
Genetic counseling is recommended for families with a history of MMA to assess the risk of recurrence.
Transplantation (liver and/or kidney) may be considered in some severe cases.
Prognosis varies depending on the severity of the deficiency and the effectiveness of treatment.