Carnitine palmitoyltransferase deficiencies

Carnitine palmitoyltransferase (CPT) deficiencies are common disorders of m itochondrial fatty acid oxidation, The CPT system is made up of two separat e proteins located in the outer- (CPT1) and inner- (CPT2) mitochondrial mem branes. While CPT2 is a ubiquitous protein, two tissue-specific CPT1 isofor ms-the so-called "liver" (L) and "muscle" (M) CPT1s-have been shown to exis t. Amino acid and cDNA nucleotide sequences have been identified for all of these proteins. L-CPT1 deficiency (13 families reported) presents as recur rent 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 for m (more than 150 families reported) is characterized by episodes of rhabdom yolysis triggered by prolonged exercise. The prevalent S113L mutation is fo und 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 bra in and kidney dysorganogenesis are frequently seen in the neonatal-onset CP T2 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 trigl ycerides and carnitine ("severe" CPT2 deficiency), Prenatal diagnosis may b e offered for pregnancies at a 1/4 risk of infantile/severe-type CPT2 defic iency. (C) 1999 Academic Press.