Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe hepatic carnitine palmitoyltransferase (CPT I) deficiency in three children (a brother and sister and their second cousin) from an extended inbred Hutterite kindred. The patients were first seen between 8 and 18 months of age with recurrent episodes of hypoketotic hypoglycemia accompanied by a decreased level of consciousness and hepatomegaly. One patient had two Reye syndrome-like episodes. Abnormal organic acids were rarely detected in urine. Serum total and free carnitine levels were elevated in all three patients. Fibroblast acyl-coenzyme A dehydrogenase activities were normal in all, but palmitic acid oxidation, performed in fibroblasts from one patient, was less than 10% of control values. Activity of CPT I in cultured skin fibroblasts from the three patients was 10% to 15% of control levels; CPT II activity was normal. Activity of CPT I and CPT II in muscle from one patient was normal. Atypical features in two of these patients were greatly elevated levels of liver enzymes and creatine kinase during acute episodes. The patients have recently been successfully treated with medium-chain triglycerides and avoidance of fasting. Early identification and treatment of this disorder may avert potentially fatal episodes of hypoglycemia.
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PMID:Atypical features of the hepatic form of carnitine palmitoyltransferase deficiency in a Hutterite family. 140 88

Since the discovery of muscle carnitine palmitoyltransferase deficiency in 1973, a dozen separate defects of mitochondrial fatty acid beta-oxidation in man have been identified. With the exception of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, which occurs with a frequency approaching 1:10,000 among Caucasians of Northern European origin, the other defects are quite rare. Collectively, however, they are common causes of disease resembling Reye syndrome in early life, and some have a later and more chronic presentation with cardiomyopathy and skeletal muscle weakness. They also represent a small, but significant, proportion of cases of sudden and unexplained death within the first 2 years of life. Diagnosis of these disorders has become increasingly sophisticated, with the advent of new analytical technologies and an increased awareness of the appropriate clinical and laboratory investigations needed in order to evaluate potential defects of this pathway. The combination of provocative testing (e.g., carnitine loading, phenylpropionic acid loading, long-chain fat loading) and advanced analytical techniques for the measurement of blood and urinary metabolites (e.g., tandem fast atom bombardment-mass spectrometry, stable isotope dilution gas chromatography-mass spectrometry) permits a specific diagnosis in the case of several, although not all, of the disorders of this pathway. Methods for the measurement of all of the enzymes of beta-oxidation are now available to enhance this diagnostic capability. There remain, however, many patients in whom clinical and laboratory signs point to a defect in beta-oxidation, but in whom no specific diagnosis has yet been made.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New developments in the diagnosis and investigation of mitochondrial fatty acid oxidation disorders. 795 87

Despite the decrease in Reye syndrome after the discontinuation of aspirin, acute encephalopathy (non-Reye syndrome type) has been continually reported in Japan. Recent studies suggested that the thermolabile phenotype of carnitine palmitoyltransferase II (CPT II) variation [F352C] was closely related to the pathomechanism of influenza-associated encephalopathy (IAE) in Japanese, causing mitochondrial ATP utilization failure during periods of high fever, resulting in brain edema. So, we analyzed CPT II polymorphism and peripheral blood ATP levels as a signal of "energy crisis" in 12 and 10 patients with acute encephalopathy, respectively. Out of the 12 patients with acute encephalopathy, six showed thermolabile CPT II variants [F352C], and of these six, two patients died in spite of intensive care. In contrast, the remaining six patients with no thermolabile CPT II variant [F352C] showed a relatively mild clinical course. Blood ATP levels of the 10 patients in the acute phase of encephalopathy were significantly lower than those during the convalescent phase and also those of patients with febrile seizure status. Our data suggest that the thermolabile F352C CPT II variant, found only in Japanese, might be one of the predisposing factors to trigger the pathomechanism of acute encephalopathy in the Japanese population, and that it is causally related to the severity of disease. The decreased blood ATP level seems to reflect systemic mitochondrial dysfunction including the blood brain barrier during the acute phase of encephalopathy.
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PMID:Thermolabile CPT II variants and low blood ATP levels are closely related to severity of acute encephalopathy in Japanese children. 2127 29