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

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

Very Long-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 Very Long-chain Acyl-CoA Dehydrogenase Deficiency is recommended.

B

OVERVIEW

During periods of prolonged fasting or increased energy demands (e.g., fever, stress, or lack of sleep), energy production increasingly relies on fat metabolism. Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) impairs energy production from fats and causes metabolic crisis, cardiomyopathy, muscle pain, or myoglobinuria. Phenotypes of VLCAD deficiency include "early," "childhood," and "adult." Sudden infant deaths may occur as a result of cardiac dysfunction or arrhythmia.

SCREENING

Finding

Elevated C14:1 +/- (acylcarnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity and specificity unknown

PREVALENCE

In the U.S., the incidence is about 1:63,000. 

INHERITANCE

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

PRENATAL TESTING

DNA testing by amniocentesis or CVS if the familial mutation is known.

MATERNAL & FAMILY HISTORY

There may be a family history of sudden infant death syndrome (SIDS).

CLINICAL CHARACTERISTICS

With treatment, risk of sudden death appears to be reduced. Without treatment, sudden cardiac death is common in the early childhood form. Symptoms of MCADD with early-onset may begin between birth and 4 months of age. Childhood onset may begin in later infancy or early childhood especially after fasting or illness. Adult onset may begin in adolescence or adulthood and may be triggered by prolonged exercise. Symptoms may be mild or severe. 

Initial signs/symptoms in the early and childhood types may include:

  • Poor feeding
  • Vomiting
  • Diarrhea
  • Irritability
  • Behavior changes
  • Extreme sleepiness
  • Muscle weakness
  • Lethargy
  • Lab findings:
  1. Metabolic acidosis
  2. Hypoglycemia

 

If not treated promptly, patients may experience:

  • Hepatomegaly
  • Difficulty breathing
  • Muscle weakness with exertion
  • Arrhythmia
  • Cardiomyopathy
  • Seizures
  • Brain damage
  • Death

EARLY SIGNS

The signs of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) can start anytime between infancy and adulthood.

Signs of a VLCADD include:

  • Sleeping longer or more often
  • Tiredness
  • Behavior changes
  • Muscle weakness (known as hypotonia)
  • Irritability
  • Poor appetite
  • Fever
  • Vomiting
  • Diarrhea
  • Low blood sugar (called hypoglycemia)

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. Other enzymes break down these fatty acids for energy. 

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

If your baby has very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), then your baby’s body is either not making enough or making non-working very long-chain acyl-CoA dehydrogenase. When this happens, your baby’s body cannot use very long chain fatty acids for energy. This is harmful because your baby needs fat for energy when there are not enough sugars to break down for energy, such as between meals. Your baby’s heart also needs fatty acids for energy.

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

TREATMENT

Dietary Treatments

Your baby will need to be on a restricted diet to avoid fats that he or she cannot break down. A dietician or nutritionist can help you plan a low-fat diet that still gives your baby the nutrients he or she needs for healthy growth and development.

Your baby will also need to eat often in order to avoid many of the signs mentioned in the Early Signs section.

Supplements

Children with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) often need dietary supplements. Medium Chain Triglyceride oil is a common supplement for individuals with VLCADD. This oil contains medium chain fatty acids, which are fats that your baby’s body can break down. Talk to your baby’s doctor before starting this type of treatment.

Your baby’s doctor might also prescribe L-carnitine supplements. L-carnitine is a substance that is naturally produced by the body, but your baby’s body might not make enough. Taking prescription L-carnitine supplements can help break down fats for energy and remove harmful substances in the body.

EXPECTED OUTCOMES

If treated early, babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) can have healthy growth and development. Treatments need to continue throughout life.

If VLCADD is not treated, babies usually die young. It is important to screen for and treat VLCADD. Untreated VLCADD can cause breathing problems, seizures, coma, or brain damage if not treated.