Muscle carnitine palmityltransferase deficiency: A case with enzyme deficiency in cultured fibroblasts

DiDonato, Stefano; Cornelio, F.; Pacini, Luca; Peluchetti, D.; Rimoldi, M.; Spreafico, S.

doi:10.1002/ana.410040513

Cited by 39 publications

(11 citation statements)

References 14 publications

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“…The modest elevations in blood lactate in one patient (M-1) suggest some abnormality in glucose metabolism, but could represent either defective hepatic gluconeogenesis or excessive glycolysis in peripheral tissues. A similar modest increase in fasting blood lactate has been noted in a patient with systemic carnitine deficiency (7). It should be noted, however, that the coma in these patients may not be entirely due to hypoglycemia: patient M-1 developed rather severe symptoms of vomiting and depressed consciousness while still normoglycemic.…”

Section: Discussionsupporting

confidence: 63%

“…In normal individuals, the % of total serum AST activity due to the mitochondrial isoenzyme has been reported to be less than 10% by investigators using the most precise techniques (19,20). The % of mitochondrial serum AST generally remains relatively constant in liver diseases associated with hepatocellular damage, such as acute and chronic viral hepatitis, fulminant hepatitis, chronic active hepatitis, and cirrhosis (7,9,13,27), but can be elevated acutely in response to hepatotoxins. Prinicd 1n (/:S.A.…”

Section: Donald M Mock'34' Marion Scott Nell I Mock and M Michamentioning

confidence: 99%

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Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Children with Non-Ketotic Hypoglycemia and Low Carnitine Levels

et al. 1983

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SummaryThe oxidation of fatty acids for energy production not only Three children in two families presented in early childhood with episodes of illness associated with fasting which resembled Reye's syndrome: coma, hypoglycemia, hyperammonemia, and fatty liver. One child died with cerebral edema during an episode. Clinical studies revealed an absence of ketosis on fasting (plasma beta-hydroxybutyrate ~0 . 4 mmole/liter) despite elevated levels of free fatty acids (2.6-4.2 mmole/liter) which suggested that hepatic fatty acid oxidation was impaired. Urinary dicarboxylic acids were elevated during illness or fasting. Total carnitine levels were low in plasma (18-25 pmole/liter), liver (200-500 nmole/ g), and muscle (500-800 nmolelg); however, treatment with Lcarnitine failed to correct the defect in ketogenesis. Studies on ketone production from fatty acid substrates by liver tissue in vitro showed normal rates from short-chain fatty acids, but very low rates from all medium and long-chain fatty acid substrates. These results suggested that the defect was in the mid-portion of the intramitochondrial beta-oxidation pathway a t the mediumchain acyl-CoA dehydrogenase step. A new assay for the electron transfer flavoprotein-linked acyl-CoA dehydrogenases was used to test this hypothesis. This assay follows the decrease in electron transfer flavoprotein fluorescence a s it is reduced by acyl-CoA--acyl-CoA dehydrogenase complex. Results with octanoyl-CoA a s substrate indicated that patients had less than 2.5% normal activity of medium-chain acyl-CoA dehydrogenase. The activities of short-chain and isovaleryl acyl-CoA dehydrogenases were normal; the activity of long-chain acyl-CoA dehydrogenase was one-third normal.

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Section: Discussionsupporting

confidence: 63%

Section: Donald M Mock'34' Marion Scott Nell I Mock and M Michamentioning

confidence: 99%

Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Children with Non-Ketotic Hypoglycemia and Low Carnitine Levels

et al. 1983

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“…The patient has been described previously (15). At the age of 12 yr, the boy first experienced muscular cramps and rhabdomyolysis after prolonged physical exercise.…”

Section: Reportsmentioning

confidence: 99%

Hepatic and Muscular Presentations of Carnitine Palmitoyl Transferase Deficiency: Two Distinct Entities

et al. 1988

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ABSTRACT. Human carnitine palmitoyl transferase (CTP) deficiency results in two different clinical variants, one with "hepatic" and one with "muscular" symptoms. We studied CPT activity and long-chain fatty acid oxidation in fibroblast cell lines from four patients, two from each group. Overall CPT activity was deficient in patients' fibroblasts with the hepatic presentation, as previously demonstrated in patients' fibroblasts with the muscular presentation. The hepatic patients' fibroblasts displayed a CPTl deficiency which resulted in impaired long-chain fatty acid oxidation. In contrast, CPTl activity and palmitate oxidation were normal in muscular patients' fibroblasts. In these latter patients, the mutation presumably involved CPT2 activity. These data suggest that CPT deficiency is due to at least two different mutations, resulting in two distinct patterns of clinical and biochemical abnormalities. (Pediatr Res 24: 308-31 1, 1988)

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“…Fibroblasts, lymphoblasts, or peripheral blood leukocytes were also collected from 59 unrelated controls and from 14 unrelated CPTase II-deficient patients with the adult muscular form [F20 (7,8), F382 (7,15) (Fig. 1).…”

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confidence: 99%

Molecular characterization of inherited carnitine palmitoyltransferase II deficiency.

Taroni

Verderio

Fiorucci

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

144

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(6, 7). Although the enzyme defect is evident in tissues other than skeletal muscle (6,8), the disease usually presents only with the muscular symptomatology. More recently, though, CPTase II deficiency has been observed also in children and newborns presenting with hypoketotic hypoglycemia, cardiomyopathy, and sudden death (9-12).These observations indicate that CPTase II deficiency is a complex disorder with phenotypic heterogeneity that may reflect underlying heterogeneity at the molecular level. As a first step to understanding the molecular basis of CPTase deficiency, we have cloned the full-length cDNA of human CPTase II (13, 14). We now report the identification and characterization of the molecular defect in a patient with the early-onset form of CPTase II deficiency presenting with hypoketotic hypoglycemia and cardiomyopathy. 16.4%, 8.8%, and 6.6% of normal control in fibroblasts, lymphoblasts, and skeletal muscle, respectively (see Fig. 4A). Fibroblast CPTase II activity was also reduced by 40%o and 35% in the father and in the mother, respectively. PATIENTS AND METHODSAbbreviations: CPTase, carnitine palmitoyltransferase; nt, nucleotide(s).tTo whom reprint requests should be addressed. 8429The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Muscle carnitine palmityltransferase deficiency: A case with enzyme deficiency in cultured fibroblasts

Cited by 39 publications

References 14 publications

Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Children with Non-Ketotic Hypoglycemia and Low Carnitine Levels

Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Children with Non-Ketotic Hypoglycemia and Low Carnitine Levels

Hepatic and Muscular Presentations of Carnitine Palmitoyl Transferase Deficiency: Two Distinct Entities

Molecular characterization of inherited carnitine palmitoyltransferase II deficiency.

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