FAQ's about MMA 

What are the symptoms of MMA?

Symptoms will present themselves at birth or later in childhood depending on the severity of the disorder. These may include: decreased muscle tone (hypotonia), failure to thrive, anorexia, delayed development, and recurrent infections with Candida sp. If not treated, catastrophic acidosis, seizures, coma and death can follow. For reasons not entirely understood, most MMA patients have no appetite and require gastronomy tube feedings.

How is MMA diagnosed?

Prior to the advent of newborn screening for this disorder, MMA was diagnosed when an infant or child failed to thrive, had trouble feeding, low muscle tone, delayed development and/or showed symptoms/lab results indicating acidosis, ketosis, or elevated ammonia. Newborn screening detects some organic acidemias and further blood tests and a skin biopsy complete the final diagnostic evaluation. Specifically, in MMA newborns, the level of propionyl carnitine is elevated. With newborn screening, babies can be rapidly treated before metabolic decompensation can occur.

What is the treatment?

Since high MMA levels are toxic, the goal of treatment is to keep these levels as low as possible yet provide enough protein (from which MMA is ultimately derived) for normal growth and development. Primarily, treatment consists of a strictly controlled diet that restricts protein and/or the four offending amino acids (isoleucine, valine, methionine and threonine). Because it is extremely difficult to measure the exact amount of protein, amino acids, fats, carbohydrates, minerals, etc. with precision in a normal diet, a special metabolic formula is prescribed. Some table foods are not restricted, however, such as lemonade, jelly, gum-drop candy or fruit.

Medications such as bicarbonate, which buffers the acid in the blood, or Flagyl (Metronidazole), which reduces the production of propionate acid in the gut, have also been used to keep MMA levels in check.

Supplements may be included depending on the type of MMA such as for extra vitamin B12 or carnitine (to speed up the removal of propionate, a precursor of MMA).

With diet restricted for protein, can MMA kids lead a normal life?

Yes. Other than diet, there are no restrictions on physical activity and many of these children attend regular school. Exercise intolerance is a reality for some, however. In general, these children happily act and appear normal. Some children require help with their feeds during school or focused instruction to help them catch up if they have developmental delays. MMA kids can and do lead normal lives, but caregivers need to be extremely careful when the child is sick.

Can they outgrow it?

No, since it is a genetic defect of metabolism.

What are the complications of MMA?

During periods of illness or stress, the body naturally speeds up its metabolism. While this poses no threat for healthy persons, for MMA kids it can put them at risk for life threatening complications. When metabolism speeds up, the body will use its own stores of muscle and fat to supply the extra energy. But muscle contains protein and its breakdown during these periods can cause acute complications such as dehydration, acidosis, hypoglycemia, hyperammonemia, seizures, encephalopathy, bone marrow suppression, pancreatitis and hepatitis. When an MMA child becomes ill (cold, flu, GI bugs, etc.) caregivers must act quickly to prevent complications, such as further restricting protein or taking them to the ER for IV medications and monitoring.

In isolated cases of MMA there is a high incidence of mental retardation and propensity toward strokes of the basal ganglia, growth problems, and renal disease.

What is meant by MMA is a “group” of metabolic disorders?

There are various forms of MMA. Some are associated with increased homocysteine. Discussion here relates to all forms. There are at least eight different complementation forms of methylmalonic acidemia:

•  Mut (0) – No methylmalonyl CoA mutase enzyme activity

•  Mut (-) - Abnormal residual activity of methylmalonyl CoA mutase enzyme

•  CblA, CblB and CblH – Defects in the pathway of adenosylcobalamin synthesis

•  CblC and CblD – Defects in the common pathway of cobalamin reduction; also has increased homocysteine

•  CblF – Defect in the lysosomal cobalamin transport; also has increased homocysteine

What is the difference between MMA and MMA Cbl-C?

MMA and Cbl-C are both (autosomal recessive) enzyme deficiencies that cause a block in the same metabolic pathway, namely the conversion of L-methyl malonyl CoA to succinyl CoA.

The enzyme missing in classical MMA is methylmalonyl CoA mutase. To do its job correctly, this methylmalonyl CoA mutase requires what is called a "cofactor" or "coenzyme" called adenosyl cobalamin, which is a derivative of vitamin B12.

Cbl-C is due to a defect in an enzyme involved in the production of this necessary cofactor, adenosylcobalamin. So some persons with methylmalonic acidemia have a mutation in one of the genes involved in cobalamin synthesis rather than in the mutase enzyme. The effect is the same except Cbl-C may also cause additional symptoms of another disorder called homocystinuria since the same cobalamin cofactor is also required in another pathway, the homocysteine metabolic pathway. (6)

6 (Personal communication, Carol Guze, medical geneticist, 2001)

Disclaimer

This information about MMA is provided by parents and is intended for awareness and information purposes only. It should not be used for diagnostic or treatment purposes. For specific medical information please contact your medical professionals.

We accept no responsibility for any errors or omissions nor do we assume any liability of any kind for the content of any information contained within this summary.