Organic acid condition(methylmalonyl-coA matase), Metabolic Disorder, Organic acid condition Screening -Infant

Organic acid condition(methylmalonyl-coA matase), Metabolic Disorder, Organic acid condition Screening -Infant

Organic acid condition(methylmalonyl-coA matase), Metabolic Disorder, Organic acid condition Screening

Summary of Recommendation and Evidence

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Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The genetic screening for Organic acid condition(methylmalonyl-coA matase) is recommended.

B

OVERVIEW

Methylmalonic acidemia is caused by a defect in methylmalonyl-CoA mutase, racemase or one of the enzymes involved in the synthesis of adenosylcobalamin, the essential cofactor of methylmalonyl-CoA mutase (cblA and cblB). Adenosylcobalamin is synthesized from vitamin B-12 through a series of reactions, some of which are shared with the synthesis of methylcobalamin (cblF, cblJ, cblC, and cblD). Defects in the proximal steps (cblF, cblJ, cblC, and some forms of cblD) result in combined methylmalonic acidemia-homocystinuria (due to defects in methionine synthase, the enzyme requiring methylcobalamin). Defects in the distal steps (some forms of cblD, cblA, and cblB) result in isolated methylmalonic acidemia. Some of these forms respond to pharmacological amounts of vitamin B-12 (provided as injectable hydroxycobalamin). The genes for all these conditions have been identified, but there are additional steps in vitamin B12 metabolism that are still unknown.

SCREENING

Finding

Elevated C3 (propionyl carnitine), elevated C4 DC (methylmalonyl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA

PREVALENCE

The prevalence of methylmalonic acidemia falls between 1:50,000 and 1:100,000.

INHERITANCE

MMA  is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

DNA testing by amniocentesis or CVS

CLINICAL CHARACTERISTICS

For MMA with treatment, some will die in the 1st year and many of the survivors will be developmentally impaired. Outcome is dependent on the severity of enzymatic impairment, with those with milder mutations (mut-) doing better than those with no residual activity (mut0). Without treatment, symptoms usually present in the first few days of life, most patients will die in the first year of life, though some will survive with deficits and a few (mut-) remain asymptomatic.  

EARLY SIGNS

Signs of methylmalonic acidemia (MUT) can start at any time from birth to adulthood. In most cases, the signs begin during infancy (either in the first few days or in the first few months of life). 

For babies, signs of MUT can include: 

  • Sleeping longer or more often 
  • Tiredness
  • Vomiting
  • Weak muscle tone (also called hypotonia)
  • Fever 
  • Breathing trouble
  • Increased number of illnesses and infections
  • Increased bleeding and bruising 

CAUSES

When we eat food, enzymes help break it down. Some enzymes break down proteins into their building blocks, amino acids. Other enzymes break down fats into their building blocks, fatty acids. More enzymes break down these amino acids and fatty acids. 

In methylmalonic acidemia, the enzyme methylmalonyl-CoA mutase is not working correctly. This enzyme helps break down odd-chain fatty acids and the amino acids isoleucine, valine, methionine, and threonine. If your baby is affected with MUT, then his or her body is either not making enough or making non-working methylmalonyl-CoA mutase enzymes. 

In “Mut 0” forms of MUT, this enzyme is completely deficient. That means that there are no working methylmalonyl-CoA mutase enzymes in the body. In “Mut –“ forms, some methylmalonyl-CoA mutase enzymes work correctly, but there are not enough. Without enough working enzymes, your baby’s body has trouble using fats and proteins for energy. 

MUT is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for MUT, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with MUT is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

There are two types of methylmalonic acidemia: cobalamin disorders and methylmalonic-CoA mutase (MUT) deficiencies. Cobalamin disorders are considered vitamin B-12 responsive. MUT deficiencies are non-vitamin B-12 responsive. You may hear about other babies with methylmalonic acidemia receiving vitamin B-12 injections. This treatment will not help a baby with methylmalonyl-CoA mutase deficiency. 

Supplements and Medications

Your baby’s doctor might recommend L-carnitine supplements. These supplements help the body break down fats, and they can remove harmful substances from the body. Your baby’s doctor will need to write a prescription for these supplements.

Antibiotics can also help reduce methylmalonic acid levels. 

Dietary Treatments 

Your baby will need a very carefully monitored diet. Children with methylmalonic acidemia need to avoid certain fats and proteins because their bodies cannot break down these substances, causing a build up of toxic substances. Your doctor can recommend special formulas and foods made for children with organic acid conditions. These formulas will likely need to be continued through adulthood.

It is also important for your baby to eat frequently. Long periods of time without food, illness, or infections may trigger many of the signs mentioned in the Early Signs section. 

EXPECTED OUTCOMES

Babies who receive treatment early on can have typical development and healthy lives. The earlier you start treatment, the better the outcome will be for your child. 

It is possible to have some long-term effects even with treatment for methylmalonic acidemia (MUT) such as learning disabilities and developmental delays.

It is important to screen for and to treat MUT. If MUT is left untreated, children can develop breathing problems or permanent brain damage.