What are the other Names for this Condition? (Also known as/Synonyms)

• Carnitine Uptake Deficiency (CUD) Disorder
• Primary Carnitine Deficiency Syndrome
• Secondary Carnitine Deficiency Syndrome

What Is Carnitine Deficiency Syndrome? (Definition/Background Information)

• Generally, during periods of fasting, the body typically turns to fats for energy production. Carnitine is the substance that helps the body use fats to produce energy. In Carnitine Deficiency Syndrome, the body’s muscle cells cannot take in carnitine, and therefore, there is limited energy source during periods of fasting
• Carnitine Deficiency Syndrome can either be primary, in which the individual is born with a genetic defect in the carnitine transporter protein; or it may be secondary, in which the individual develops the condition because of other metabolic disorders
• The signs and symptoms of Carnitine Deficiency Syndrome may include irritability, fatigue, abnormal liver enlargement, and failure to thrive in children. The possible complications from the syndrome include organ damage (liver and heart) and severe brain dysfunction
• Carnitine Deficiency Syndrome can be diagnosed during newborn screening to detect low carnitine levels in blood and high carnitine levels in urine. Molecular testing and/or functional studies (which test carnitine uptake in cell culture) allow for confirmation of Carnitine Deficiency Syndrome diagnosis

·The treatment of Carnitine Deficiency Syndrome involves administration of carnitine supplements and symptomatic treatment, along-with lifestyle changes and dietary control. The prognosis is generally good with early and appropriate management of the condition

Who gets Carnitine Deficiency Syndrome? (Age and Sex Distribution)

• The age of onset is during infancy/early childhood and affects males and females equally
• There does not appear to be any racial or geographical distributions associated with Carnitine Deficiency Syndrome

What are the Risk Factors for Carnitine Deficiency Syndrome? (Predisposing Factors)

• A family history of the disorder is a risk factor for Primary Carnitine Deficiency Syndrome
• Certain metabolic disorders may increase one’s risk for Secondary Carnitine Deficiency Syndrome
• Presently, no other risk factors are established for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Carnitine Deficiency Syndrome? (Etiology)

• Carnitine Deficiency Syndrome is a metabolic muscle disease that is characterized by an interference with fat processing needed for the production of energy (fat metabolism that turns fat into energy)
• Carnitine Deficiency Syndrome can be either primary or secondary:
  • This condition is caused by a genetic defect in the protein (carnitine transporter protein) that is responsible for transporting carnitine into the cell. This is known as Primary Carnitine Deficiency Syndrome. This condition is inherited in an autosomal recessive manner
  • Secondary Carnitine Deficiency Syndrome can also occur, in which case it develops because of other metabolic disorders in the body

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Carnitine Deficiency Syndrome?

• The main signs and symptoms of Carnitine Deficiency Syndrome include low muscle tone and muscle weakness in the neck and jaw, shoulders and upper arms, hips and legs, and even in the heart. These symptoms occur if the disorder is confined to the muscles only
• However, if the disorder affects the body’s tissues, typically in severe cases, additional signs and symptoms may be noted such as:
  • Nausea and vomiting
  • Irritability
  • Fatigue
  • Abdominal pain
  • Low blood sugar (hypoglycemia)
  • Failure to thrive in children
  • Low weight gain
  • Abnormal liver enlargement
  • Abnormal brain function

How Is Carnitine Deficiency Syndrome Diagnosed?

In order to diagnose Carnitine Deficiency Syndrome, a complete family history and thorough physical examination is performed.

• Assessment of the presenting signs and symptoms is important
• Blood and urine tests, as necessary
• Radiological imaging studies of the affected parts of the body
• Prenatal imaging studies
• If carnitine levels in blood are extremely low after molecular genetic testing is performed, a healthcare provider may suspect Carnitine Deficiency Syndrome. The genetic testing is performed primarily to identify mutations in a specific gene (the SLC22A5 gene)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible Complications of Carnitine Deficiency Syndrome?

• Complications of Carnitine Deficiency Syndrome include organ damage to the liver, heart, brain, and various skeletal muscles of the body, including heart muscle weakness (cardiomyopathy)
• Brain injury may present severe brain dysfunction (encephalopathy), irreversible learning problems, and mental retardation
• Another complication includes problems with the metabolism of the body, especially relating to fat and energy metabolism. The body’s cells cannot take in fats since carnitine acts as a “ferry” to bring in fats. Without a receptor to bring in carnitine, fat metabolism is compromised in the body
• Emotional stress and decreased quality of life

How Is Carnitine Deficiency Syndrome Treated?

The most important methods of treatment of Carnitine Deficiency Syndrome include maintaining stable carnitine levels in blood and managing hypoglycemia associated with the syndrome.

• To keep carnitine levels stable, L-carnitine (an amino acid derivative used in the body for energy metabolism) is administered. This supplementation is especially effective if the individual starts treatment before organ/tissue damage occurs
• To avoid low blood sugar, dextrose (a sugar) is given through intravenous administration. Maintaining a proper diet is also important to avoid low blood sugar levels
• Treatment of Carnitine Deficiency Syndrome is geared towards minimizing complications in metabolism and in various organs, including the liver, heart, and muscles
• In the case of cardiomyopathy (enlarged heart), a cardiologist may be involved in treatment of the condition

How can Carnitine Deficiency Syndrome be Prevented?

Currently, Primary Carnitine Deficiency Syndrome may not be preventable since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

The prevention of Secondary Carnitine Deficiency Syndrome involves suitably treating the underlying metabolic disorder with which it is associated.

What is the Prognosis of Carnitine Deficiency Syndrome? (Outcomes/Resolutions)

The onset of Carnitine Deficiency Syndrome is in early infancy/childhood and continues into adulthood.

• The condition progresses slowly, but overall has a good prognosis, if early treatment is begun before organ damage occurs, and if proper treatment plan is adhered to
• While mental retardation is irreversible if it occurs, most complications of Carnitine Deficiency Syndrome are generally controlled, once prompt and appropriate treatment is provided

Additional and Useful Relevant Information for Carnitine Deficiency Syndrome:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/rare-disorders/