The Severe Metabolic Condition Known As Primary Carnitine Deficiency And Its Genetic Cause

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What Is Primary Carnitine Deficiency?

Primary carnitine deficiency (PCD) is a genetic disorder which is marked by abnormal body metabolism. Specifically, those who suffer from PCD either cannot metabolize fats in a manner that allows them to be converted into energy or they metabolize so poorly that little energy is produced. Normally, in the fat conversion process, cells use carnitine, which is a compound that is present in most foods, to help carry out the process. In individuals who are affected with PCD, defects in, or absence of, a protein that normally serves to shuttle carnitine within cells prevents the fat-to-energy conversion process from being properly carried out.

The failure to properly metabolize fats can lead to many severe symptoms. For example, PCD-affected individuals typically experience one or more of the following:

  • brain injury (which often affects all regions of the brain and causes problems such as confusion and reduced intellectual ability)
  • an swollen heart that has a reduced capacity to pump blood
  • reduced blood sugar levels (hypoglycemia)
  • muscle fatigue
  • nausea and vomiting

In the worst cases, heart failure, coma, and even death can result. Symptoms often become exacerbated whenever the PCD sufferer does not eat enough or becomes inflicted with a viral infection. Unfortunately, options for treating PCD symptoms are limited, which means that PCD sufferers are largely at the mercy of the disorder.

Although PCD is relatively rare outside of the Japanese population (it affects an estimated 1 in every 100,000 non-Japanese individuals), it is somewhat more common among Japanese people (about 1 in every 40,000 Japanese individuals suffers from PCD).

What Is Known About The Genetics of Primary Carnitine Deficiency?

It has long been known that PCD is inherited in an autosomal recessive fashion. In recent years, a team of Japanese human molecular biologists discovered that PCD is caused by mutations in a gene that is referred to as SLC22A5. The SLC22A5 gene encodes a protein that is known as OCTN2. In healthy individuals, the OCTN2 protein is localized to the cell membrane, where it functions to transport carnitine from the bloodstream and into the cells in which it is needed to help convert fat to energy. Primarily, cells that require carnitine (and therefore OCTN2) are those that are found in the brain, kidney, heart and skeletal muscle tissue.

Individuals who have PCD, and therefore who have one or mutations in both copies of their OCTN2 genes, either do not make OCTN2 or they make a defective version of this protein. In either case, the lack of properly functioning OCTN2 leads to the inability to shuttle carnitine from the blood and into the cells in which it is needed.

This article is only meant to provide some basic information regarding the genetic condition known as primary carnitine deficiency. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.


Genetics Home Reference, National Institutes of Health, Primary carnitine deficiency:

Genetics Home Reference, National Institutes of Health, SLC22A5:

J. Nezu et al., Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter, Nature Genetics 21:91-94 (1999).