Carnitine Uptake Defect/Carnitine Transport Defect, Metabolic Disorder, Fatty acid oxidation disorder Screening -Infant

Summary of Recommendation and Evidence

Population	Recommendation	Grade (What's This?)
Screening of both genders	The genetic screening for Carnitine Uptake Defect/Carnitine Transport Defect is recommended.	B

Carnitine Uptake Defect/ Carnitine Transport Defect is a rare metabolic disorder in which the body cannot properly process fats into energy. Carnitine functions to carry fatty acids obtained through diet to the energy centers in muscle cells (mitochondria). A deficiency of carnitine results in accumulation of fats in the liver, muscle, and heart.

OVERVIEW

Carnitine uptake deficieny (CUD) results in urinary carnitine wasting and systemic and intracellular carnitine deficiency. The latter results in an intramitochondrial defect in the beta-oxidation of fatty acids that impairs energy production and causes accumulation of free fatty acids. The increased reliance on fat metabolism for energy production during prolonged fasting and/or periods of increased energy demands (fever, stress, lack of sleep) may cause metabolic crises in patients with carnitine deficiency. Mutations in the SLC22A5 gene cause CUD. This gene is responsible for making a protein called OCTN2 that transports carnitine into cells.

SCREENING

Finding

Decreased C0 and other acylcarnitines (C3, C16, C18)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100% (80% with the first screen only); specificity=99.97%

PREVALENCE

Approximately 1 in 40,000 ,with about 1% of the normal US population being heterozygous (carriers) for this condition.

INHERITANCE

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

PRENATAL TESTING

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Gunctional assay (carnitine transport) possible by amniocentesis or CVS.

OTHER TESTING

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

CLINICAL CHARACTERISTICS

With treatment prior to metabolic crises, outcomes should be normal. Treatment may reverse pre-existing cardiomyopathy and muscle weakness, but not developmental delay. Without treatment, symptoms may begin between birth and three years of age or, in the myopathic form, symptoms usually begin before seven years and may not include metabolic crisis episodes or hypoglycemia. Some children remain asymptomatic for life. Patients are at risk of sudden death from arrhythmia at any age.

Inital signs and symptoms may include:

poor appetite
·vomiting
irritability
lethargy
hypoketotic hypoglycemia
sudden death
Lab findings:
1. anemia
2. metabolic acidosis
3. hypoglycemia

Subsequent finding include:

muscle weakness
cardiomyopathy
cardiac arrhythmia
hepatomegaly
seizures and
brain injury from hypoglycemia

EARLY SIGNS

The first signs of carnitine uptake defect (CUD) usually begin between birth and 3 years of age. These signs vary from child to child. Your baby may show many of them or none at all.

Signs of CUD include:

Sleeping longer or more often
Tiredness
Irritability
Poor appetite
Fever
Vomiting
Diarrhea
Low blood sugar (called hypoglycemia)
Behavior changes
Confusion
Breathing troubles

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. The carnitine transporter enzyme is very important for breaking down fats. This enzyme's job is to move carnitine into the mitochondria of the cell. Mitochondria are the energy-making factories of cells.

If your baby has carnitine uptake defect (CUD), then your baby’s body either does not make enough of or makes non-working copies of the carnitine transporter. When this happens, your baby’s body cannot use fats for energy. This is harmful because your baby’s heart needs fats for energy. Your baby’s body also needs fats for energy when his or her body runs out of sugars to break down, such as between meals.

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

TREATMENT

Supplements

Prescription L-carnitine supplements is the main treatment for carnitine uptake defect (CUD). L-carnitine is a substance that is naturally produced in the body, but your baby’s body might not make enough of it. These supplements help break down fats and get rid of harmful waste substances that build up in the body. Your baby’s doctor will need to write you a prescription for these supplements.

Dietary Treatment

Your baby will probably need to follow a restricted diet in order to avoid eating fats that his or her body cannot break down. A nutritionist or a dietician can help you plan your baby’s diet.

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

EXPECTED OUTCOMES

Carnitine uptake defect (CUD) is easily treated. Children who receive treatment early on have healthy growth and development.

Even if your baby has not received treatment yet, L-carnitine can often reverse the heart troubles and muscle weakness that often result from CUD.

If CUD is not treated, children are at risk of heart trouble, liver damage, breathing problems, or even permanent brain damage. This is why early screening and treatment are so important.