Carnitine palmitoyltransferase 1 deficiency

Carnitine palmitoyltransferase deficiency is an autosomal recessive myopathy caused by a genetic defect of the mitochondrial enzyme CPT (Fig. 42-2). The disease is prevalent in men (male female ratio, 5.5 1) and appears to be the most common cause of recurrent myoglobinuria in adults [4]. 

Pande, S.V. Murthy, M.S.R. (1990) Biochim. Biophys. Acta, 1044, 262-268. Freeze-thawing causes masking of membrane-bound outer carnitine palmitoyltransferase activity implications for studies on carnitine palmitoyltransferases deficiency. 

DiMauro, S. DiMauro, P.M. (1973) Muscle carnitine palmitoyltransferase deficiency and myoglobinuria. Science 182 929-930. 

Zierz, S. (1994) Limited trypsin proteolysis renders carnitine palmitoyltransferase insensitive to inhibition by malonyl-CoA in patients with muscle carnitine palmitoyltransferase deficiency. Clin Invest 72 957-960. 

Schaefer, J., Jackson, S., Taroni, F., Swift, P. Turnbull, D.M. (1997). J Neurol Neurosurg Psychiatry 62 169-176. Characterisation of carnitine palmitoyltransferases in patients with a carnitine palmitoyltransferase deficiency implications for diagnosis and therapy. 

DiMauro S, Papadimitriou A. Carnitine palmitoyltransferase deficiency. In Engel A, Banker B, editors. Myology basic and clinical. New York McGraw-HiU 1986. p. 1697. 

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

In 1955, Fritz determined that carnitine plays an essential role in fatty acid -oxidation (FAO), and in 1973 the first two clinically relevant disorders affecting this pathway were described primary carnitine deficiency by Engel and Angelini, and carnitine palmitoyltransferase (CPT) type II (CPT-II) deficiency by DiMauro and DiMauro [6, 7]. To date, more than 20 different enzyme deficiency states affecting fatty acid transport and mitochondrial / -oxidaLion have been described [8] and additional enzymes involved in this pathway are still being discovered [9, 10]. 

What effect would a deficiency of carnitine palmitoyltransferase in skeletal muscle have on the ability of a person to perform prolonged exercise ... 

Clinical problems related to fatty acid metabolism. Deficiencies in carnitine lead to an inability to transport fatty acids into the mitochondria for oxidation. This can occur in newborns and particularly in pre-term infants. Treatment is by oral carnitine administration. Carnitine palmitoyltransferase I (CPT I) deficiency primarily affects the liver and leads to reduced fatty acid oxidation and ketogenesis. CPT II deficiency results in recurrent muscle pain, fatigue and myoglobinuria following strenuous exercise. 

Carnitine palmitoyltransferase II deficiency is a metabolic disorder characterised by an... 

M. R. Pierce, G. Pridpan, S. Morrison, and A. S. Pickoff Fatal carnitine palmitoyltransferase II deficiency in a newborn New phenotypic features. Clinical Pediatrics 38, 13 (1999). 

Wieser, T, Dechauer, M. Zierz, S. (1998) Carnitine palmitoyltransferase II deficiency three novel mutations. Ann. Neurol. 42 414-415. 

The mitochondrial outer membrane enz5mie carnitine palmitoyltransferase 1 (CPTl) is a main site of regulation of intracellular long-chain fatty acid transport. At least two isoforms of CPTl are expressed in the body L-CPTl (the liver-type isoform) and M-CPTl (the muscle-type isoform). Skin fibroblasts from healthy humans are known to contain only one isoform of CPTl the liver-type, which is encoded by the gene CPTIA. Skin fibroblasts from patients with a liver-type CPTl deficiency do not express either of the two known CPTl isoforms (neither liver- nor muscle-t3T)e), and therefore could provide an excellent background to study CPTl by means of molecular complementation. 

Carnitine-acylcarnitine translocase deficiency Carnitine palmitoyltransferase type II deficiency 2... 

Hug, G. Soukoup, S. l99l)NewEngl J. Med. 325, 1862-1864 Lethal neonatal multiorgan deficiency of carnitine palmitoyltransferase II. 

Trevisan, C.P. Angelini, C. Freddo, L. Isaya, G. Martinuzzi, A. (1984) Neurology 34, 353-356 Myoglobinuria and carnitine palmitoyltransferase (CPT) deficiency studies with malonyl-CoA suggest absence of only CPT-II. 

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