Methylmalonic acidemia (MMA) is a rare genetic disorder with an incidence of one in 50,000 live births, affecting males and females from all demographics. MMA was first identified in 1967. In MMA, the body is unable to break down certain amino acids namely methionine, threonine, isoleucine and valine which leads to the inability in properly digesting specific fats and proteins, leading to build up of a toxic level of methylmalonic acid in blood and disrupts the normal amino acid metabolism. Symptoms of MMA include poor feeding, vomiting, trouble in breathing, and lethargy. [1,2]



Methylmalonic acidemia is inherited in an autosomal recessive pattern.[3] In MMA, one copy of the altered gene is inherited from the mother and the other copy of the altered gene is inherited from the father. Therefore, each parent of an affected child has one copy of the gene that is altered and one that is unaltered. Parents are called “carriers”. Carriers are asymptomatic. MMA is a major concern in countries such as Palestine where immediate family members often marry and have children that inherit MMA at a much higher prevalence than neonates in western countries.[3]



There are different types of MMA. The types of MMA which can be treated with vitamin B12 injections are called ‘vitamin B12 responsive.’ The other type, called ‘MMA with homocystinuria’ occurs when   special enzymes which change vitamin B12 into a form that the body can use is either missing or not working properly. As a result homocystine, methylmalonic acid, and other harmful substances  build up in the blood.[4]



MMA is diagnosed at birth through newborn screening ­– a simple heel stick blood sample at birth used to check for numerous diseases. MMA is typically confirmed when proteins are introduced in the infant’s diet. The presence of MMA can also be suspected through the use of a CT or MRI scan or ammonia test. Elevated levels of ammonia, glycine, and ketone bodies may also be present in the blood and urine. However, these tests are by no means specific and require clinical and metabolic/correlation.[5]

Additional tests for MMA diagnosis include:

  • Biochemical testing for abnormal levels of specific chemicals
  • Testing for responsiveness to vitamin B12
  • Genetic testing for mutations in one of the genes associated with methylmalonic acidemia.[5]




One such case is of a child from Children’s Hospital of Philadelphia. In less than 24 hours of being brought home, the baby had trouble eating and breathing. The baby was unable to open his eyes and the arms would flop. The temperature was critically low and neonatologists found dangerously high levels of ammonia in his system. MMA was diagnosed through newborn screening. His condition was treated through medications and a special diet low in protein.[6]



Currently, one of the main treatment is a diet low in the amino acids leucine, valine, methionine, and threonine with limited amounts of protein. There are also specially formulated foods such as special low-protein flours, pastas, rice and snacks such as biscuits that are made especially for children with organic acid disorders.[7]

A liver transplant or a combination kidney-liver transplant is another alternative treatment used to treat MMA when repeated metabolic decompensation cannot be relieved by medication or nutrition therapy. Transplantation helps to prevent metabolic crises, lowers plasma and MMA levels in the urine, and also enhances overall quality of life. Even though the surgery is known to be lifesaving, it does not totally cure the disorder. Majority of the patients still maintain a low protein diet even after the surgery.[8]



On May 29, 2021, a 9-year-old patient, Eddie Axelson, of Monroe Carell Jr. Children’s Hospital at Vanderbilt was the first in the world to receive an investigational gene editing therapy for MMA. Axelson received the dose of hLB-001, administered via IV infusion. In gene editing therapy, a harmless virus is used to transport the missing gene into liver cells, so that the liver cells will start producing the deficient enzyme to correct the defect in body chemistry.[9]



  1. Methylmalonic acidemia. (2021, August 15). Wikipedia.
  2. Methylmalonic acidemia: MedlinePlus Genetics. (n.d.).
  3. Methylmalonic acidemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. (2016).
  4. Clark, P. A., & Myers, A. T. (2017, August 11). To Treat or Not To Treat: The Case of Methylmalonic Acidemia.
  5. MMA (methylmalonic acidemia) – (n.d.). Retrieved September 6, 2021, from
  6. Philadelphia, T. C. H. of. (2014, March 30). Methylmalonic Acidemia: Gavin’s Story.
  7. About Methylmalonic Acidemia. (n.d.).
  8. Jiang, Y.-Z., & Sun, L.-Y. (2019). The Value of Liver Transplantation for Methylmalonic Acidemia. Frontiers in Pediatrics,
  9. Echegaray, C. (2021, June 3). Patient of Monroe Carell Jr. Children’s Hospital at Vanderbilt first in world to receive new investigational gene editing therapy. Vanderbilt University.


Meghna Ravi
Pristine Organics