Carnitine Palmitoyltransferase Deficiencies

doi:10.1006/mgme.1999.2938

Molecular Genetics and Metabolism

Volume 68, Issue 4, December 1999, Pages 424-440

https://doi.org/10.1006/mgme.1999.2938 Get rights and content

Abstract

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.

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¹: To whom correspondence should be adressed at Groupe Hospitalier Necker-Enfants Malades, Tour Lavoisier 2 étage, 149, rue de Sèvres 75743, Paris Cedex 15, France. Fax: 33 / 1/ 44 49 51 50. E-mail: [email protected].

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MinireviewCarnitine Palmitoyltransferase Deficiencies

Abstract

Biochim Biophys Acta

J Lipid Res

J Biol Chem

J Biol Chem

J Biol Chem

FEBS Lett

FEBS Lett

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Neurol Sci

J Biol Chem

Genomics

Genomics

FEBS Lett

J Biol Chem

J Pediatr

J Pediatr

J Neurol Sci

J Pediatr

J Neurol Sci

Am J Med

Biochem Biophys Res Commun

J Neurol Sci

FEBS Lett

Neuromusc Disord

Neuromusc Disord

The mitochondrial carnitine palmitoyltransferase system

Eur J Biochem

Immunoquantitative analysis of human carnitine palmitoyltransferase I and II defects

Pediatr Res

Human liver mitochondrial carnitine palmitoyltransferase I characterization of its cDNA and chromosomal localization and partial analysis of the gene

Proc Natl Acad Sci USA

Defects in activation and transport of fatty acids

J Inher Metab Dis

A mitochondrial carnitine acylcarnitine translocase system

Proc Natl Acad Sci USA

Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane

Proc Natl Acad Sci USA

More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic β-cell signaling

Diabetes

Comparison of the active sites of the purified carnitine acyltransferases from peroxisomes and mitochondria by using a reaction-intermediate analogue

Biochem J

cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase

Proc Natl Acad Sci USA

Carnitine palmitoyltransferase 1, the site of inhibition of hepatic fatty acid oxidation by malonyl-CoA

J Biol Chem

Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation

Biochem J

Hepatic and muscular presentations of carnitine palmitoyltransferase deficiency: Two distinct entities

Pediatr Res

Carnitine palmitoyltransferase II deficiency: Structure of the gene and characterisation of two novel disease-causing mutations

Hum Molec Genet

Expression of liver carnitine palmitoyltransferase I and II genes during development in the rat

Biochem J

Expression of novel isoforms of carnitine palmitoyltransferase I (CPT-I) generated by alternative splicing of the CPT-Ib gene

Biochem J

Carnitine palmitoyltransferase 1 deficiency presenting as a Reye-like syndrome without hypoglycemia

Eur J Pediatr

Deficiency of carnitine palmitoyltransferase I

J Child Neurol

Elevated plasma carnitine in the hepatic form of carnitine palmitoyltransferase 1 deficiency

J Inher Metab Dis

Renal tubular acidosis in carnitine palmitoyltransferase type 1 deficiency

N Engl J Med

Rate-dependent distal renal tubular acidosis and carnitine palmitoyltransferase I deficiency

Pediatr Res

Minireview
Carnitine Palmitoyltransferase Deficiencies