Carnitine palmitoyltransferase (
CPT) deficiencies are common disorders of mitochondrial
fatty acid oxidation. The
CPT system is made up of two separate
proteins located in the outer- (CPT1) and inner- (CPT2) mitochondrial membranes. While CPT2 is a ubiquitous
protein, two tissue-specific CPT1
isoforms-the so-called "liver" (L) and "muscle" (M) CPT1s-have been shown to exist.
Amino acid and
cDNA nucleotide sequences have been identified for all of these
proteins. L-CPT1 deficiency (13 families reported) presents as recurrent attacks of fasting hypoketotic
hypoglycemia. Two L-CPT1 mutations have been reported to date. M-CPT1 deficiency has not been hitherto identified.
CPT2 deficiency has several clinical presentations. The "benign" adult form (more than 150 families reported) is characterized by episodes of
rhabdomyolysis triggered by prolonged exercise. The prevalent S113L mutation is found in about 50% of mutant alleles. The infantile-type
CPT2 deficiency (10 families reported) presents as severe attacks of hypoketotic
hypoglycemia, occasionally associated with cardiac damage commonly responsible for
sudden death before 1 year of age. In addition to these symptoms, features of brain and kidney dysorganogenesis are frequently seen in the neonatal-onset
CPT2 deficiency (13 families reported), almost always lethal during the first month of life. More than 25 CPT2 mutations (private missense or truncating mutations) have hitherto been detected. Treatment is based upon avoidance of fasting and/or exercise, a
low-fat diet enriched with medium chain
triglycerides and
carnitine ("severe"
CPT2 deficiency). Prenatal diagnosis may be offered for pregnancies at a 1/4 risk of infantile/severe-type
CPT2 deficiency.