Several important proteins are involved when cells break down fats to provide energy to the body. This process happens inside the mitochondria, also called the “Powerhouse of the Cell,” which are small, enclosed “little organs” (organelles) in cells. Carnitine palmitoyltransferase 1a (CPT1a) functions as a sentry in the liver and other tissues, where it controls the amount of fat that can enter the mitochondria to be used to produce needed energy. If CPT1a is lost, reduced or functions poorly, the fatty acid cannot cross the mitochondrial inner membrane to where it is used to make energy.
The severe forms of CPT1a deficiency usually show up early in infancy when an infant is stressed by fasting or illness. The most common symptom is low blood sugar (hypoglycemia) with low levels of ketones (hypoketosis). Ketones are made by the body when fat is used for energy. If the fat cannot be used for energy, such as in CPT1a deficiency, few ketones will be made. Severe hypoglycemia and hypoketosis can lead to coma and seizures. Build-up of the unused fats in the liver can cause the liver to function poorly, become enlarged (hepatomegaly) and fail. Other organs can fail, as well, but skeletal muscles are not affected. Some children with milder forms of CPT1a may never develop these dangerous symptoms.
Most cases of CPT1a deficiency in the United States are identified through newborn screening of bloodspots collected in the first few days of life. Following a newborn screen suggestive of CPT1a, additional specialized testing will be needed to confirm the diagnosis. Rarely, diagnosis in a fetus can be made during pregnancy if the mother experiences a life-threatening syndrome called HELLP syndrome (this includes red blood cell breakdown, abnormal liver function and decreased blood clotting). Cells obtained from the amniotic fluid or during chorionic villus sampling (CVS; a biopsy of the placenta)) can be used to detect CPT1a or similar disorders in the fetus.
CPT1a is a genetic disorder. It occurs when a child inherits a mutation in the gene for CPT1a from each carrier parent. A couple in which both parents are carriers for CPT1a have a 25% chance with each pregnancy of having another child with this genetic disorder. While the severe form is very rare, a mild CPT1a defect is found frequently in the Inupiaq and Yu’pik and the Inuit nations in Alaska and Canada, as well as in Hutterite populations. The gene change found in the Inupiaq and Yu’pik populations may give a survival advantage to people in the arctic, so it is considered a variant rather than a mutation. Even so, infants inheriting the variant can develop dangerously low blood sugar during illnesses.
Regular feeding and prevention of fasting is the mainstay of CPT1a therapy. Feedings are closely spaces, every 2-3 hours, to start. In severe cases, continuous feeding by a stomach tube may be necessary, especially at night. Medium chain triglyceride (MCT) oil and artificial fats may be helpful when given as a supplement because the body uses them differently to make energy. As children grow older, they will typically become more stable and can usually go longer between feedings.
Mildly ill children with low CPT1a should be given liquids that contain glucose or sugars frequently. Parents should call their health care provider immediately whenever these infants become excessively sleepy, are vomiting, have diarrhea, a fever, poor appetite, or an infection. In hospital, these children will be given sugar by vein to provide energy.