Methylmalonic Acidemia: Causes, Symptoms, and Treatment
Medically reviewed by Harsha Moole, MD, Internal Medicine. Last reviewed: October 23, 2026.
What kind of doctor treats Methylmalonic Acidemia?
A biochemical geneticist, a doctor who treats inherited metabolic diseases, usually leads care for methylmalonic acidemia, along with a pediatrician, a children's doctor. A direct primary care or concierge doctor can be a first stop for an evaluation and can refer you to a specialist when needed.
What is methylmalonic acidemia?
Methylmalonic acidemia is a group of inherited disorders that prevent the body from breaking down proteins and fats properly. A substance called methylmalonic acid builds up in the blood.
The effects vary from mild to life-threatening. It is rare. It occurs in an estimated 1 in 50,000 to 100,000 people.
Symptoms
The first signs usually appear in early infancy. Babies may look normal at birth. They develop symptoms once they start eating more protein, which can make the condition worse. Affected infants can have:
- Vomiting and dehydration, which means the body has too little water.
- Weak muscle tone, called hypotonia.
- Developmental delays.
- Being very tired, called lethargy.
- An enlarged liver.
- Trouble gaining weight and growing at the expected rate.
The disease can also cause seizures and stroke. Some babies have brain damage that gets worse over time.
People with this condition can have frequent episodes of too much acid in the blood, called metabolic acidosis. These episodes cause serious health problems. Without treatment, the disorder can lead to coma and death in some cases.
Long-term problems can include feeding problems, intellectual disabilities, movement problems, chronic kidney disease, and inflammation of the pancreas.
Causes and who gets it
Changes in genes cause this condition. The genes named are MMUT, MMAA, MMAB, MMADHC, and MCEE. About 60 percent of people with it have a change in the MMUT gene.
The MMUT gene tells the body how to make an enzyme, a protein that helps chemical reactions. The enzyme is called methylmalonyl-CoA mutase. It works with vitamin B12 to break down protein building blocks, certain fats, and cholesterol. When it does not work well, methylmalonic acid and other harmful compounds build up in the body.
The MMAA, MMAB, and MMADHC genes help the body make and control vitamin B12. The most severe form is called mut0.
The condition is passed down in an autosomal recessive pattern. That means a child needs a changed copy of the gene from each parent. The parents each carry one changed copy but usually have no symptoms. When both parents are carriers, the chance of an affected child is 25% with each pregnancy.
It affects boys and girls equally. It is most often diagnosed in the first year of life.
How doctors diagnose it
Testing for it is often done as part of a newborn screening exam. The condition can be found at birth on a blood spot. Screening at birth is recommended by the US Department of Health and Human Services because early detection and treatment is helpful.
Tests that may be done to diagnose the condition include:
- Blood ammonia test.
- Blood electrolyte levels and blood gases.
- Methylmalonic acid blood test.
- Plasma amino acid test.
- A CT scan or MRI of the brain.
- Genetic testing.
More testing on blood, urine, and sometimes skin is needed to confirm the diagnosis. Genetic testing for changes in the five named genes can also confirm it.
Treatment
Treatment includes a low-protein diet and supplements of cobalamin (vitamin B12) and carnitine. The child's diet must be carefully controlled. The diet also includes special formulas, medical foods, and regular meals and snacks.
If supplements do not help, the provider may recommend a diet that avoids four amino acids, the building blocks of protein. They are isoleucine, threonine, methionine, and valine.
Liver or kidney transplants have been shown to help some children. The new organ gives the body cells that break down methylmalonic acid normally.
A low-protein diet can help reduce the number of attacks. People with this condition should avoid people who are sick with contagious illnesses, such as colds and the flu. Genetic counseling is recommended for families of an affected child.
Children who are treated early in life may still have learning difficulties and intellectual disability. Babies may not survive their first episode of symptoms.
When to see a doctor
Contact your child's provider if your child is not gaining weight as expected or has developmental delays.
Call 911 or go to the emergency room if your child has a seizure, trouble breathing, bluish or grey skin, vomiting that keeps happening, will not feed, or is very sleepy and hard to wake.
How a direct primary care or concierge doctor fits in
A direct primary care doctor charges a flat monthly fee instead of billing insurance, while a concierge doctor usually charges more and often works alongside insurance. A direct primary care doctor can help watch your child's weight gain and development. They can also help your family get genetic counseling.
Common questions
Is methylmalonic acidemia inherited?
Yes, it is passed down through families. It is an autosomal recessive condition. This means the changed gene must be passed to the child from both parents.
Can newborn screening find methylmalonic acidemia?
Yes, it can. The condition can be identified at birth on a blood spot through expanded newborn screening.
Can methylmalonic acidemia be treated?
Yes. Dietary changes and supplements can prevent some of the harmful effects of this disorder. Treatment also includes a low-protein diet. Some children still have learning difficulties even when treated early.
How common is methylmalonic acidemia?
It is rare. It occurs in an estimated 1 in 50,000 to 100,000 people.
Sources
- MedlinePlus - Methylmalonic acidemia
- MedlinePlus Genetics - Methylmalonic acidemia
- NORD - Methylmalonic Acidemia
Medical Disclaimer
This content is for general educational and informational purposes only and is not medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment, and reading it does not create a doctor-patient relationship. Always seek the advice of your physician or another qualified health provider with any questions about a medical condition, and never disregard or delay seeking professional advice because of something you read here. If you think you may have a medical emergency, call 911 (or your local emergency number) immediately.
