Methylmalonic acidemia (MMA)| Fatal Genetic Disorder | Autosomal Recessive Disorder

 

Methylmalonic acidemia or MMA is generally a rare and fatal genetic disorder which affects metabolism and body systems that usually affects about 1 in 100,000 infants. Generally, these defects are caused by a genetic defect which prevents the body from processing proteins from foods you eat.

People who have this health condition are unable to produce an enzyme which is needed to break down. This health condition causes a buildup of acids and other toxic substances in the blood, urine and other cells which includes brain cells other than creating proteins from your foods. Usually, this disease will mostly be diagnosed within a few months of life.

But, how this toxic substance buildup will affect the body and it can vary drastically from one person to another person. For some people, this health condition can cause severe long term problems like seizures, strokes, growth problems, developmental delays and frequent severe illness.

This metabolic defect leads to buildup of methylmalonic acid in the body. Methylmalonic acidemia will cause serious symptoms like coma if it is not treated and diagnosed correctly.

Causes

Generally, this Methylmalonic acidemia disorder belongs in the group of disorders called inborn errors of metabolism.

Metabolism helps the body convert nutrients in the food into energy. Inborn errors of metabolism are caused by various genetic defects which lead to problems with metabolism.

Usually, this disorder is mostly diagnosed in the first year of life, that is after 1 year of birth. It means that defective genes must be passed into the child from both the biological parents.

Newborns with this rare and fatal disorder may die before it is diagnosed. Methylmalonic acidemia conditions will affect both girls and boys equally.

Symptoms of Methylmalonic Acidemia

Methylmalonic acidemia is generally a complex disorder which causes a variety of symptoms. The intensity of these symptoms will vary which is based on the exact genetic mutation that causes the disease.

For example, an infant or newborns are undergoing a decompensation, they may experience:

• Difficulty breathing

• Muscle weakness

• Vomiting

• Low energy like lethargic

• Low body temperature

• Decreased consciousness

Methylmalonic acidemia disease will lead to severe long-term health problems, such as:

• Intellectual disability

• Pancreatitis

• Poor appetite and growth

• Seizures

• Osteoporosis

• Kidney disease and it may cause kidney failure

• Optic nerve atrophy will cause vision problems

• Sudden stroke of brain region called basal ganglia which causes movement problems

• Blood problems like lower number of certain immune cells and anemia

Exams and Tests

Methylmalonic acidemia test often done as part of newborn screening exam. The United States Department of Health and Human Services suggest screenings for this illness at birth because early detection and treatment is helpful.

Some test that may be performed to diagnose this disorder includes:

• Ammonia test

• Blood gases

• Complete blood count

• CT scan or MRI of the brain

• Electrolyte levels

• Genetic testing

• Methylmalonic acid blood test

• Plasma amino acid test

Treatment

Treatment mainly focuses on managing the symptoms. People who have MMA disease must follow a specific low-protein diet. Some specific medications and antibiotics can be a part of treatment plan and people with a particular variation of the disease can benefit from vitamin B12 supplements.

In some rare cases, liver transplantation will help the children with methylmalonic acidemia to lead a normal life. The healthy transplanted liver produces enzymes which process the dietary proteins. In some rare cases, people with MMA will also require kidney transplant.

Emergency Treatment

Intensive support in a hospital setting is necessary in emergency situations.

Some immediate things might be needed during an emergency which includes:

• Intravenous (IV) fluids

• Glucose (sugar) administration

• bacterial infection treatment

• Strict protein diet for intake

• IV carnitine therapy

• Breathing support

•  to remove toxic byproducts, you can use Hemodialysis or extracorporeal membrane oxygenation (ECMO)

New Potential Treatments

Researchers and scientists are also investigating advanced and new treatments for methylmalonic acidemia, some advanced treatments like gene therapy and antioxidant treatments. 

Ask your provider if you are interested in participating in a clinical trial. Or, you have to check the database of United States clinical trials.

Possible Complications

Some Complications are:

• Coma

• Death

• Kidney failure

• Pancreatitis

• Cardiomyopathy

• Recurrent infections

• Hypoglycemia

Prevention

A low-protein diet will help you to reduce the number of attacks. People with MMA should avoid contacting people who are sick with contagious illnesses like colds and the flu. Genetic counseling will be more helpful for couples who have a family history of this disorder and who wish to have a baby.

Sometimes, for newborns screening tests will be expanded at birth especially for methylmalonic acidemia. You must ask your doctor if your child underwent this screening or not.

Monitoring

People with MMA need regular monitoring for long-term life-threatening complications of this disorder. For example, this condition includes regular monitoring of your eye exams and kidney function tests.

Ideally, people with methylmalonic acidemia should visit a specialist who has experience in rare genetic diseases. This disease required medical professionals working together as a team for treatment and monitoring.

Frequently Asked Questions

Q1. What are the signs and symptoms of methylmalonic acidemia?

Ans: Symptoms may include lethargy, failure to thrive, recurrent vomiting, acidosis, dehydration, respiratory distress, diminished muscle tone, developmental retardation, seizures and/or an enlarged liver.

Q2. What is the most common cause of methylmalonic acidemia?

Ans: About 60 percent of methylmalonic acidemia cases are caused by mutations in the MMUT gene. 

Q3. What is the life expectancy of someone with methylmalonic acidemia?

Ans: The prognosis of MMA is varied and fluid. Depending on severity, life-expectancy and quality-of-life range from days to years.

Q4. How is MMA diagnosed?

Ans: A definitive diagnosis of the disorder is based on urine organic acid analysis using gas chromatography/mass spectrometry (GC/MS).

Q5. Is MMA increased in B12 deficiency?

Ans: If your body doesn't have enough vitamin B12, it will make extra amounts of MMA. High MMA levels can be a sign of a vitamin B12 deficiency.