Carnitine is a common molecule that is required to carry certain fats into the mitochondria, where these “powerhouses of the cell” convert them into energy. Carnitine is transported into the cells by a protein called OCTN2, which is essential to maintaining carnitine levels throughout the body. When this protein is missing or fails to function normally, the cells develop a condition called primary carnitine transporter deficiency. Without OCTN2, dietary carnitine cannot enter the blood and any carnitine made by the body is filtered out by the kidney and lost through urine.
Children commonly show symptoms of OCTN2 deficiency between the ages of three months and two years, usually after a minor illness such as a stomach virus or an ear infection. Infants become extremely sleepy and difficult to wake, are irritable, refuse to eat, and have poor muscle tone. Clinically, they usually have low blood sugar (hypoglycemia) with low ketones (hypoketotic) and an enlarged, poorly functioning heart (dilated cardiomyopathy) and liver damage. Older children and adults may have an enlarged heart, and progressive muscle weakness with fat deposits in muscle, accompanied by a mild increase in creatine kinase, a muscle damage indicator. Occasionally, this disorder in the fetus can cause a dangerous form of fluid accumulation called fetal hydrops.
Newborn screening by tandem mass spectrometry of blood spots is the most common method for beginning the diagnostic process for primary carnitine transporter deficiency. While there are other fatty acid disorders where carnitine levels can be low, only infants with this condition have no dicarboxylic acids in their urine. If necessary, the carnitine defect can analyzed in tissues such as cultured skin cells (fibroblasts) or white blood cells (lymphoblasts). Molecular testing of the OCTN2 gene (SLC22A5) is clinically available. Testing can also be performed on tissues or cultured cells (amniocytes) from a fetus, if a defect is suspected.
However, this diagnosis can be complicated since the mother provides carnitine to the fetus during pregnancy. If the blood for the newborn screening is taken too soon, an affected infant may have a supply of leftover carnitine from the mother. On the other hand, newborn screenings have identified several mothers with a mild form of the defect, including some without symptoms. For this reason, the carnitine status of the mother is an essential part of the diagnosis whenever low carnitine is found on newborn screening.
Children with carnitine transporter deficiency inherit one defective SLC22A gene from each parent. With each pregnancy, the parents have a 25% risk chance to have another child with the same SLC22A mutations. Siblings of the affected person should be tested for SLC22A defects, in case a diagnosis was missed. Primary carnitine transporter deficiency is rare in the United States, occurring in approximately 1 in 100,000 newborns. In Japan, this disorder affects 1 in every 40,000 newborns.
Primary carnitine transporter deficiency is treated by giving large doses of L-carnitine to the patient. In emergency situations, the fluids can be given intravenously, followed by larger oral doses for the rest of the patient’s life. If the patient develops a fishy odor, oral metronidazole can be added to the regimen. A patient with cardiomyopathy or other heart problems will need specialized cardiac treatment.
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