Carnitine Uptake Defect (Primary Carnitine Deficiency)

Introduction

The carnitine uptake defect (CUD), caused by a lack of the primary carnitine transporter (OCTN2), is a rare inherited fatty acid oxidation disorder (FAOD). When OCTN2 is lost, the body cannot use most fats to make energy to run the body. In the United States, the defect is rare and occurs in approximately 1 in 100,000 newborns. In the Japanese CUD is much more common, affecting 1 in every 40,000 newborns. CUD is one of several genetic disorders where the body cannot produce energy from fats. As a group these are called fatty acid oxidation disorders (FAODs). At the International Network of Fatty Acid Oxidation Research and Management (INFORM) Center, our goal is to educate the public about FAODs and to create a support group community that helps families of those with CUD and other FAODs.

What is Carnitine?

Carnitine is a small molecule found in nearly every cell in the body. It must be attached to most fats for them to enter into mitochondria, the powerhouses of the cell. Once inside, these fats are broken down to generate energy to run the body. Carnitine is transported into cells by a protein named OCTN2.

What is a CUD (Carnitine Uptake Defect)

Our Fatty Acid Oxidation Research shows that when OCTN2 is missing or fails to function normally, dietary carnitine cannot enter the blood, and even the small amount of carnitine that the body can make is filtered out by the kidney and lost through urine. When there is not enough active OCTN2, the cells develop a condition called primary carnitine transporter deficiency, known as CUD.

Is Primary Carnitine Defect (CUD) Genetic?

The gene that makes OCTN2 is known as SLC22A. Children with the carnitine transporter deficiency inherit one defective SLC22A gene from each parent. With each pregnancy, the parents have a 25% chance that their child will inherit both of the SLC22A mutations and develop the fatty acid oxidation disorder CUD as a result. Blood siblings of the affected person should be tested for SLC22A defects in case a diagnosis was missed at birth.

Signs and Symptoms of Carnitine Uptake Defect

Children commonly show symptoms of the OCTN2 deficiency or primary carnitine defect (CUD) between the ages of three months and 7 years, usually after a minor illness such as a stomach virus or an ear infection. The most common signs of primary carnitine transporter deficiency in children include:

  • Always tired and difficult to wake up
  • Irritable
  • Refuses to eat
  • Muscles are weak (poor tone)
  • Blood sugar is low (hypoglycemia)
  • Ketones are low (hypoketotic)
  • Heart is enlarged or poorly functioning (dilated cardiomyopathy)
  • Liver has damage

Signs in Older Children and Adults with Carnitine Uptake Defect

Older children and adults will show other signs of the carnitine uptake defect (CUD) including:

  • Enlarged heart
  • Gradually developing muscle weakness with fat deposits in muscle
  • Mildly increased creatine kinase (a muscle damage indicator)

It is important to note that occasionally, primary carnitine deficiency can cause fetal hydrops, a dangerous form of fluid accumulation in the baby that occurs before birth.

How to Diagnose Carnitine Uptake Defect (CUD)

The most common method for identifying suspected CUD is by newborn screening for carnitine by tandem mass spectrometry. For this test, a small spot of the infant’s blood is placed on a paper card. Infants with CUD will have very low carnitine levels in their blood, and their urine will also lack a second group of fat products called dicarboxylic acids. To make certain that the infant has the defect, the laboratory may want to repeat the diagnostic analysis in tissues from the baby such as cultured skin cells (fibroblasts) or white blood cells (lymphoblasts). Molecular testing of the OCTN2 gene (SLC22A5) is clinically available, if necessary.

Testing for CUD can also be performed on tissues or cultured cells (amniocytes) from a fetus if a defect is suspected before the child is born. This diagnosis can be more complicated because the mother provides carnitine to the fetus during pregnancy. Similarly, if the blood for newborn screening is taken too soon, an affected infant may have a supply of leftover carnitine from the mother. In this case, when the test misses the defect, it is known as a false negative. On the other hand, several mothers with a mild form of the defect, including some without symptoms have been identified through low carnitine levels in their newborn infants. For this reason, the carnitine status of the mother is an essential part of the diagnosis whenever low carnitine levels are found on newborn screening.

Treatment of CUD or Primary Carnitine Deficiency

Primary carnitine transporter deficiency is treated by giving large doses of L-carnitine supplements by mouth, as prescribed by a licensed professional. This large dose of L-carnitine increases the amount of carnitine both in the body fluids and inside of cells. In emergency situations, L-carnitine supplements can be given in intravenous fluids. These large oral doses of L-carnitine will be required for the rest of the patient’s life. Sometimes the L-carnitine supplement causes the patient to develop a fishy odor. This odor is harmless and can be reduced by adding oral metronidazole to the treatment. Patients who develop cardiomyopathy or other heart problems from CUD will need additional specialized cardiac treatment.

Other Names for Primary Carnitine Deficiency

  • Carnitine transporter deficiency
  • Carnitine uptake defect
  • Carnitine uptake deficiency
  • CUD
  • Renal carnitine transport defect
  • Systemic carnitine deficiency
  • OCTN2 deficiency

Investigational Therapies

Like other FAODs, information on current clinical trials can be found at Clinical Trials, a database of privately and publicly funded clinical studies conducted around the world. Studies include those receiving government funding as well as some supported by private industry.

If you or someone you love is affected by these fatty acid oxidation disorders (FAOD), INFORM Network is here to help you as you cope through the process. At our Fatty Acid Oxidation Research and Management (INFORM) Center, we aim to support families and friends impacted by FAOD, providing the community with resources and FAOD support groups. Our founder, Jerry Vockley, has made it his mission to share credible information about fatty acid oxidation disorders and to raise awareness of these very rare disorders, such as carnitine uptake defect (CUD), CACT deficiency, multiple acyl-Coa dehydrogenase deficiency, and a number of others.

Further Information

At INFORM Network we aim to promote more research on these rare disorders as well as spread awareness through education of FAOP and be a huge resource for those impacted by these disorders.

Have more questions? Contact us today by giving us a call at 412-692-5099 or send us an email at keith.mcintire@chp.edu.

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