Background
Carnitine uptake defect (CUD) is a condition that prevents the body from using fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through diet, is used by cells to process fats and produce energy. In people with CUD, proteins called carnitine transporters do not work properly. These proteins normally bring carnitine into cells and prevent the escape of carnitine from the body in urine. CUD is estimated to occur in less than 1 of 100 000 live births. However it has been reported to have an incidence rate of 1:40 000 live births in Japan.
Clinical
Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and often include changes in brain tissue (encephalopathy) resulting in functional abnormalities; an enlarged, poorly pumping heart (cardiomyopathy); confusion; vomiting; muscle weakness; and low blood sugar (hypoglycemia). Serious complications such as heart failure, liver problems, coma, and sudden unexpected death are also a risk. Severe illness due to CUD can be triggered by periods of fasting or illnesses such as viral infections, particularly when eating is reduced.
This condition is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu.
Testing
Newborn screening using tandem mass spectrometry of a dried blood spot identifies low level of free carnitine (C0). (C0+C2+C3+C16+C18:1+C18)/Cit is also found as informative ratio. Plasma and urine carnitine analysis will reveal decreased free and total carnitine (C0) in plasma and overexcretion of carnitine in urine. The newborn’s mother should be investigated, as well, because several cases of maternal CUD have been identified following an abnormal newborn screening result in their offspring. Transporter assays and OCTN2 gene sequencing establish the diagnosis.
Treatment
Treating CUD patients with oral L-carnitine supplementation is followed by a slow increase of plasma carnitine levels. If the infants’ levels reflect maternal primary carnitine deficiency, the rise in plasma levels is fast and this should prompt the work-up towards the diagnosis of maternal primary carnitine deficiency. CUD patients should also avoid fasting and sometimes low-fat, high carbonhydrate diet is used in addition to L-carnitine. Guidelines for the management of carnitine deficiency and other fatty acid mitochondrial disorders have been established.
Because the diagnosis and therapy of CUD is complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician.
Inheritance
This disorder follows an autosomal recessive inheritance pattern. With recessive disorders affected patients usually have two copies of a disease gene (or mutation) in order to show symptoms. People with only one copy of the disease gene (called carriers) generally do not show signs or symptoms of the condition but can pass the disease gene to their children. When both parents are carriers of the disease gene for a particular disorder, there is a 25% chance with each pregnancy that they will have a child affected with the disorder.