CUD: Carnitine Uptake Defect

Carnitine uptake defect is a type of genetic condition where a small molecule called carnitine is not able to do its job of helping fats enter the mitochondria (our powerhouse cells) where they can be broken down to create energy. This prevents the body from creating enough energy during times of stress, illness, fasting, and exercise, which can lead to medical symptoms. The body usually gets its energy by breaking down, or burning, fats and sugars. People with FAODs cannot properly break down certain types of fats.

Systemic Primary Carnitine Deficiency

CUD

CDSP

SLC22A5

• Autosomal recessive

People usually have two copies of the SLC22A5 gene, one inherited from each parent. CUD occurs when there are changes in both copies of the SLC22A5 gene (autosomal recessive inheritance). Someone who has a change in only one copy of the SLC22A5 gene is called a carrier, and they usually do not have any medical symptoms. If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will have CUD.

1:100,000

In Japan, CUD is much more common and occurs in approximately 1 in every 40,000 newborns

Both Male and Female

CUD can cause a range of signs and symptoms. Whether your child was diagnosed via newborn screening may also affect when, if, and how these symptoms present.  Always check with your doctor if your child is doing something out of “their” normal, as every child may present with symptoms a little differently.

CUD usually presents between the ages of three months to seven years after an episode of minor illness like a stomach virus or ear infection, but older children and adults can also be diagnosed. Signs and symptoms may include:

• Irritability
• Extreme tiredness (lethargy)
• Refusing to eat
• Weak muscles and poor muscle tone (hypotonia)
• Low blood sugar (hypoglycemia)
• Low ketones (hypoketotic)
• Enlarged, weakened heart (dilated cardiomyopathy)
• Liver damage
• Mildly high creatine kinase (sign of muscle damage)
• Gradual increase of muscle weakness
• Fat deposits in the muscle
• Intravenous (IV) sugar-containing fluids called D10 during metabolic crisis

In some cases, CUD can cause fetal hydrops, a dangerous form of fluid buildup in a baby that occurs before birth.

Most cases of CUD are identified by routine newborn screening. If newborn screening is suggestive of CUD, additional tests may be performed including:

• Repeat testing on cultured skin cells (fibroblasts) or white blood cells (lymphoblasts)
• Genetic testing to look for changes in the SLC22A5 gene

In some cases, a diagnosis can be made before birth if there is a known family history of CUD or if a baby has fetal hydrops. This testing can be complicated because mothers provide carnitine to babies during pregnancy.

If there is a family history of CUD, or if parents are known carriers, prenatal testing can be performed.

Yes

Treatment and management of CUD may include:

• L-carnitine supplements
• Routine management of heart conditions

Sometimes an L-carnitine supplement causes people with CUD to develop a fishy odor. This odor is harmless and can be reduced by adding a medicine called metronidazole to the treatment.

Parents should call their healthcare provider immediately if babies show symptoms like excessive sleepiness, vomiting, diarrhea, a fever, poor appetite, or an infection. Medical treatment should be sought immediately if there is loss of consciousness or severe confusion (decompensation), as these are signs of dangerously low blood sugar.

Patients should discuss the appropriate preparation for anesthesia with their metabolic team.

• Primary carnitine deficiency – About the Disease – The National Institutes of Health
• CUD Deficiency | Fatty Acid Oxidation Disorders Diagnosis – The INFORM Network
• Systemic Primary Carnitine Deficiency – National Organization for Rare Disorders (NORD)

Connecting with others impacted by a rare disease allows for vital information to be shared about day-to-day life, prevents isolation, and gives hope. Please contact MitoAction for peer support opportunities at 888-MITO-411 or email mito411@mitoaction.org.

Other resources we recommend are:

• New Patient Kit for Mitochondrial Conditions
• Planning and Preparation
• Monthly Expert Series
• Energy in Action Podcast