Medium-chain Acyl-CoA Dehydrogenase Deficiency, Metabolic Disorder, Fatty acid oxidation disorder Screening -Infant

Medium-chain Acyl-CoA Dehydrogenase Deficiency, Metabolic Disorder, Fatty acid oxidation disorder Screening -Infant

Medium-chain Acyl-CoA Dehydrogenase Deficiency, Metabolic Disorder, Fatty acid oxidation disorder Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both genders

The genetic screening for Medium-chain Acyl-CoA Dehydrogenase Deficiency is recommended.

B

OVERVIEW

Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is one of several enzymes involved in the beta-oxidation of fatty acids within mitochondria. MCADD impairs hepatic ketogenesis, resulting in hypoketotic hypoglycemia during periods of prolonged fasting or increased energy demands (e.g., during acute illness or fever).

SCREENING

Finding

Elevated C8 (octanoylcarnitine) with lesser elevations of C6 (hexanoylglycine) and C10:1 (decenoyl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.98%

PREVALENCE

Prevalence is about 1:17,759 live births; it is most common in northern Europeans and US Caucasians.

INHERITANCE

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

PRENATAL TESTING

Amniocentesis or chorionic villous sampling (CVS) for DNA testing

CLINICAL CHARACTERISTICS

With treatment, prognosis is excellent. Without treatment, episodes of hypoketotic hypoglycemic accompanied by lethargy and vomiting may lead to seizures, coma, cardiac arrest, and death. Symptoms can appear shortly after birth (sometimes just after hospital discharge) or at time of acute illness, which prevents the child from eating or causes increasing energy expenditure (fever). Some affected individuals do not present until adulthood. 

Initial symptoms/signs may include:

  • Poor feeding
  • Vomiting
  • Lethargy progressing to coma
  • Lab findings:
  • Hyperammonemia
  • Hypoglycemia
  • Elevated ALT and AST

 

Subsequent symptoms/signs may include:

  • Hepatomegaly
  • Liver dysfunction
  • Seizures
  • Encephalopathy
  • Sudden death

EARLY SIGNS

The first signs of medium-chain acyl-CoA dehydrogenase deficiency (MCAD) usually begin during infancy or early childhood (three months to three years of age). You might see signs such as:

  • Sleeping longer or more often
  • Tiredness
  • Behavior changes
  • Irritable mood
  • Poor appetite
  • Fever
  • Diarrhea
  • Low blood sugar (referred to as hypoglycemia)
  • Vomiting

Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

CAUSES

When we eat food, enzymes help break it down. Certain enzymes help break down fats into their building blocks, fatty acids.

Fatty acids are built like chains and come in many lengths. They are categorized as either short, medium, long, or very long. Different enzymes work on breaking down different lengths of fatty acids. An enzyme called medium-chain acyl-CoA dehydrogenase is in charge of breaking down medium-length fatty acids. If you have a question about what makes a fatty acid “medium” length.

If your baby has medium-chain acyl-CoA dehydrogenase deficiency (MCAD), your baby’s body either does not make enough or makes non-working medium-chain acyl-CoA dehydrogenase enzymes. When this happens, your baby cannot use medium-length fatty acids for energy. This is harmful because your baby’s body needs fat for energy when his or her body runs out of sugars (such as between meals). The heart also needs fatty acids for energy.

MCAD is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for MCAD, 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 MCAD is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Dietary Treatment

Your baby will need to be on a restricted diet to avoid the types of fats your baby’s body cannot break down. A dietician or a nutritionist can help plan a high-carbohydrate, low-fat diet that still gives your baby the nutrients he or she needs for healthy growth.

Eating often will also help prevent your baby from experiencing many of the signs mentioned in the Early Signs section.

Supplements and Medication

Your baby’s doctor might prescribe L-carnitine supplements. L-carnitine is a substance that most individuals make naturally, but your baby’s body might not be making enough of it. Prescription L-carnitine helps your baby’s body break down fats and remove harmful substances.

EXPECTED OUTCOMES

Children who receive early treatment for medium-chain acyl-CoA dehydrogenase deficiency (MCAD) have healthy growth and development.

If MCAD is not treated, children may experience breathing problems, seizures, liver troubles, brain damage, coma, and possibly death. Early screening and treatment can avoid these effects.