Summary about Disease
Methylmalonic acidemia (MMA) is a rare inherited metabolic disorder in which 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, urine, and tissues. There are different types of MMA, caused by different genetic defects, each affecting how the body processes methylmalonic acid. The severity of MMA varies widely among affected individuals.
Symptoms
Symptoms can vary widely, even within the same type of MMA, and can appear in infancy or later in life. Common symptoms include:
Poor feeding
Vomiting
Lethargy (extreme tiredness)
Seizures
Developmental delay
Failure to thrive (poor weight gain and growth)
Hypotonia (poor muscle tone)
Enlarged liver (hepatomegaly)
Kidney problems
Breathing problems
Coma
Causes
MMA is caused by genetic mutations (changes) in genes that provide instructions for enzymes needed to process methylmalonic acid. These enzymes are involved in the metabolism of certain amino acids (building blocks of protein) and fats. The most common causes are mutations in the MUT gene (methylmalonyl-CoA mutase), the *MMAA* gene, *MMAB* gene, *MMACHC* gene, and *MMADHC* gene. These mutations lead to a deficiency or complete absence of the necessary enzyme activity. MMA 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 for MMA is focused on managing symptoms and preventing complications. Medications commonly used include:
Vitamin B12 (hydroxocobalamin): Some forms of MMA respond to high doses of vitamin B12.
L-Carnitine: Helps remove harmful organic acids.
Antibiotics: To reduce the production of propionic acid by gut bacteria.
Sodium benzoate or sodium phenylacetate: To help remove excess ammonia from the body.
Is Communicable
No, methylmalonic acidemia is not communicable. It is a genetic disorder, meaning it is caused by inherited gene mutations and cannot be spread from person to person.
Precautions
Precautions for individuals with MMA and their families focus on managing the condition and preventing metabolic crises:
Dietary Management: Following a strict, low-protein diet is crucial to reduce the buildup of harmful substances. This often involves a special medical formula and careful monitoring by a metabolic dietician.
Emergency Protocol: Having a detailed emergency protocol for handling metabolic crises (e.g., during illness or stress) is vital. This should include instructions on when to seek medical attention, what medications to administer, and what dietary adjustments to make.
Regular Monitoring: Regular blood and urine tests are necessary to monitor methylmalonic acid levels and kidney function.
Genetic Counseling: Genetic counseling is recommended for families affected by MMA to understand the risk of recurrence in future pregnancies.
Avoidance of Prolonged Fasting: Prolonged fasting can trigger metabolic crises.
How long does an outbreak last?
MMA is not an infectious disease, it is a genetic condition. Affected individuals do not have "outbreaks". They may experience episodes of metabolic crisis, where symptoms acutely worsen due to a buildup of toxic metabolites. The duration of a metabolic crisis varies, but can last from several days to weeks. Factors that influence the duration include the severity of the episode, the promptness of treatment, and the individual's overall health.
How is it diagnosed?
Diagnosis of MMA typically involves:
Newborn Screening: Many states include MMA in their newborn screening programs, which involves testing a blood sample for elevated levels of methylmalonic acid and other markers.
Urine Organic Acid Analysis: This test identifies abnormal levels of organic acids, including methylmalonic acid, in the urine.
Blood Amino Acid Analysis: Detects elevated levels of certain amino acids.
Plasma Acylcarnitine Profile: Detects elevated levels of certain acylcarnitines.
Genetic Testing: Confirms the diagnosis by identifying mutations in the genes known to cause MMA.
Enzyme Assay: Measures the activity of the methylmalonyl-CoA mutase enzyme in cultured fibroblasts.
Prenatal Testing: If there is a family history of MMA, prenatal testing (amniocentesis or chorionic villus sampling) can be performed to determine if the fetus is affected.
Timeline of Symptoms
The timeline of symptoms in MMA is variable, depending on the type and severity of the condition:
Neonatal Onset: Some infants develop symptoms within the first few days or weeks of life, including poor feeding, vomiting, lethargy, and seizures.
Late-Onset: Other individuals may not develop symptoms until later in infancy, childhood, or even adulthood. These individuals may have milder symptoms, such as developmental delay, failure to thrive, or kidney problems.
Episodic: Regardless of the age of onset, individuals with MMA may experience episodic metabolic crises, triggered by illness, stress, or changes in diet. These crises can cause a rapid worsening of symptoms.
Important Considerations
Lifelong Management: MMA is a lifelong condition that requires ongoing medical management, including dietary restrictions, medications, and regular monitoring.
Neurological Complications: Untreated or poorly managed MMA can lead to serious neurological complications, such as developmental delay, intellectual disability, and seizures.
Kidney Disease: Kidney disease is a common complication of MMA and can progress to kidney failure.
Pancreas Problems: Pancreatitis can also occur in some individuals.
Early Diagnosis and Treatment: Early diagnosis and treatment are crucial to minimize the long-term complications of MMA.
Support Groups: Support groups and online resources can provide valuable information and emotional support for individuals with MMA and their families.