Methylmalonic Acidemia (MMA) Clinical Trials and Treatments

Methylmalonic acidemia encompasses several genetic defects that disrupt the conversion of methylmalonyl-CoA to succinyl-CoA, a critical step in the breakdown of branched-chain amino acids (isoleucine, valine, methionine, threonine), odd-chain fatty acids, and cholesterol. The most severe forms involve complete deficiency of methylmalonyl-CoA mutase (mut0 subtype) or defects in adenosylcobalamin synthesis (cblA, cblB subtypes). Toxic accumulation of methylmalonic acid, propionylcarnitine, and related metabolites causes acute metabolic decompensation (metabolic acidosis, hyperammonemia, hypoglycemia) during periods of catabolism such as illness, fasting, or surgery.

The most common symptoms of Methylmalonic Acidemia include Metabolic crises with severe vomiting, lethargy, and dehydration (often triggered by illness or fasting), Failure to thrive and poor growth in infancy, Developmental delay and intellectual disability, Chronic kidney disease progressing to renal failure, Low muscle tone (hypotonia) and movement abnormalities, among others. Methylmalonic Acidemia affects approximately 1 in 50,000 to 100,000 live births in the U.S.; identified through newborn screening in all 50 states. Symptoms can range from mild to severe and may vary between individuals.

Trial Friend lists all active clinical trials for Methylmalonic Acidemia from ClinicalTrials.gov, with eligibility criteria translated into plain English. Patients can filter by trial phase and recruitment status, search by location, and use the Match Me tool to score trials against their profile. Gene therapy for MMA is one of the most closely watched programs in metabolic disease. The NIH MMA-101 trial (Phase 1/2) is evaluating an AAV8 vector delivering the MMUT gene to the liver in children ages 3 to 18 with the mut0 subtype.

As of September 2026, Trial Friend's curated drug index does not include an FDA-approved treatment specific to Methylmalonic Acidemia. The Treatments section of this page checks FDA drug labels live and lists any approved drug whose label names the condition, and the trials listed below cover the investigational options.

Methylmalonic Acidemia is caused by variants in the MMUT, MMAA, MMAB, MMADHC and MCEE genes. About 60% of isolated MMA is MMUT (methylmalonyl-CoA mutase); MMAA, MMAB, and MMADHC affect vitamin B12 cofactor handling and are often B12-responsive.

It is inherited in an autosomal recessive pattern: both parents are usually unaffected carriers, and each pregnancy has a 1 in 4 chance of an affected child. The condition affects approximately 1 in 50,000 to 100,000 live births in the U.S.; identified through newborn screening in all 50 states. Genetic testing confirms the diagnosis.

Yes. Genetic testing for Methylmalonic Acidemia looks at the MMUT, MMAA, MMAB, MMADHC and MCEE genes. About 60% of isolated MMA is MMUT (methylmalonyl-CoA mutase); MMAA, MMAB, and MMADHC affect vitamin B12 cofactor handling and are often B12-responsive.

It is inherited in an autosomal recessive pattern: both parents are usually unaffected carriers, and each pregnancy has a 1 in 4 chance of an affected child.

A confirmed variant establishes the diagnosis and is often required to enroll in gene-specific trials. The labs currently offering the test are listed in the Genetic Testing section of this page, pulled live from the NIH Genetic Testing Registry. A genetic counselor can help interpret the result and decide which relatives should be tested.

Eligibility for Methylmalonic Acidemia clinical trials depends on factors like age, diagnosis, treatment history, and overall health. Each trial sets its own inclusion and exclusion criteria. Trial Friend translates these requirements from medical language into plain English so patients can review them more easily. The Match Me tool can score your profile against active trials to help identify studies that may be a fit.

Participating in a Methylmalonic Acidemia clinical trial typically involves scheduled visits, medical tests, and close monitoring by a research team. Depending on the study phase, you may receive an investigational treatment, a placebo, or the current standard of care. Trials may last from a few weeks to several years. Study participation is voluntary, and you can withdraw at any time.