M J Bennett
Affiliation: University of Texas Southwestern Medical Center
- Impaired mitochondrial fatty acid oxidative flux in fibroblasts from a patient with malonyl-CoA decarboxylase deficiencyM J Bennett
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, USA
Mol Genet Metab 73:276-9. 2001..These results suggest that there is inhibition of fatty acid oxidation in malonyl-CoA decarboxylase deficiency and that this inhibition may be related to some of the clinical phenotypes...
- Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiencyMichael J Bennett
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9072, USA
Mol Genet Metab 82:59-63. 2004..Because there are no easily recognizable disease-specific metabolite markers, diagnostic confirmation of this disorder requires a combination of enzymatic analysis and whole gene sequencing...
- Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid beta-oxidationP M Jones
University of Texas Southwestern Medical Center, Department of Pathology, and Children s Medical Center of Dallas, TX 75235, USA
Clin Chem 46:149-55. 2000..We describe a serum/plasma assay for the measurement of 3-OH-FAs with carbon chain lengths from C(6) to C(16)...
- Accumulation of free 3-hydroxy fatty acids in the culture media of fibroblasts from patients deficient in long-chain l-3-hydroxyacyl-CoA dehydrogenase: a useful diagnostic aidP M Jones
University of Texas Southwestern Medical Center, Department of Pathology, Dallas, TX 75235, USA
Clin Chem 47:1190-4. 2001..The diagnosis of long-chain L-3-hydroxy-acyl-coenzyme A dehydrogenase (LCHAD) deficiency frequently requires the study of cultured fibroblasts. We developed such a test that does not require disruption and loss of the cells...
- Inborn errors of mitochondrial fatty acid oxidationM J Bennett
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA
Crit Rev Clin Lab Sci 37:1-44. 2000..In this review, we provide an overview of the pathway, discuss the disorders that are well established, and describe recent advances in the field. Currently available diagnostic procedures are critically evaluated...
- Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzymeN F Brown
Departments of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA
J Lipid Res 42:1134-42. 2001..The demonstration of L-CPT I deficiency in this patient suggests that the spectrum of clinical sequelae associated with loss or alteration of L-CPT I function may be broader than was previously recognized...
- Fatal hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency: clinical, biochemical, and pathological studies on three subjects with this recently identified disorder of mitochondrial beta-oxidationM J Bennett
Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA
Pediatr Dev Pathol 2:337-45. 1999..This is the initial pathological characterization of this enzyme defect, and our observations suggest that SCHAD deficiency is a very severe disorder contributing to early infant death...
- Cloning and mutational analysis of human malonyl-coenzyme A decarboxylaseJ Gao
The Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
J Lipid Res 40:178-82. 1999..The genetic mutation underlying malonyl CoA decarboxylase deficiency was determined in a patient with clinical features of this defect, malonic aciduria, and markedly reduced malonyl CoA decarboxylase activity...
- Regulation of biologically active dimeric inhibin A and B from infancy to adulthood in the maleW Byrd
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235 9032, USA
J Clin Endocrinol Metab 83:2849-54. 1998..Because this glycoprotein is secreted in high amounts in the prepubertal testis up to 3 yr of age, inhibin B could potentially be used as a marker in the diagnosis of cryptorchidism and precocious puberty...
- Quantitative measurement of total and free 3-hydroxy fatty acids in serum or plasma samples: short-chain 3-hydroxy fatty acids are not esterifiedP M Jones
Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, USA
J Inherit Metab Dis 23:745-50. 2000..This finding has important implications for the use of the acylcarnitine assay for the diagnosis of defects involving short-chain and medium-chain 3-hydroxy fatty acids...
- Mitochondrial short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency: a new defect of fatty acid oxidationM J Bennett
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, 75234, USA
Pediatr Res 39:185-8. 1996..In isolated fibroblast mitochondria the residual enzyme activities were 5 and 6% of the normal controls. Activity in an obligate heterozygote was intermediate, suggesting that this is an autosomal recessive disorder...
- CLN-3 protein is expressed in the pancreatic somatostatin-secreting delta cellsR L Boriack
Department of Pathology, Children's Medical Center of Dallas, 1935 Motor Street, Dallas, Texas 75235, USA
Eur J Paediatr Neurol 5:99-102. 2001..This staining showed localization in pancreatic islet cells. Double labelling of the tissue indicated that cells staining for the CLN3 protein were also positive for somatostatin...
- Evidence for fatty acid oxidation in human placenta, and the relationship of fatty acid oxidation enzyme activities with gestational ageD Rakheja
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Placenta 23:447-50. 2002....
- Tissue expression and subcellular localization of CLN3, the Batten disease proteinL R Margraf
Department of Pathology, University of Texas Southwestern Medical Center and Children s Medical Center of Dallas, Dallas, Texas 75235, USA
Mol Genet Metab 66:283-9. 1999..PPT was most abundant in brain and visceral macrophages where it displayed a coarse granular staining pattern typical of lysosomal distribution. Immunoelectron microscopy confirmed that PPT immunoreactivity was limited to lysosomes...
- Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutationsUte Spiekerkoetter
Department of Pediatrics and Vanderbilt Children s Hospital, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
Hum Mutat 21:598-607. 2003..The degree of reduction in thiolase antigen also correlated with the severity of clinical presentation. Although TFP deficiency is highly heterogeneous, there is genotype-phenotype correlation...
- Effects of odd-numbered medium-chain fatty acids on the accumulation of long-chain 3-hydroxy-fatty acids in long-chain L-3-hydroxyacyl CoA dehydrogenase and mitochondrial trifunctional protein deficient skin fibroblastsPatricia M Jones
Department of Pathology, University of Texas Southwestern Medical Center, Children s Medical Center of Dallas, Dallas, TX 75235, USA
Mol Genet Metab 81:96-9. 2004..We found that provision of odd-chain species does decrease the build-up of long-chain FAO intermediates in our in vitro skin fibroblast model, but to a lesser extent than even-numbered MCFAs...
- Hydrolethalus syndrome, in contrast to Smith-Lemli-Opitz syndrome, is not due to a defect in post-squalene cholesterol biosynthesis: a case reportDinesh Rakheja
Am J Med Genet A 129:212-3. 2004
- Identification of 16 new disease-causing mutations in the CPT2 gene resulting in carnitine palmitoyltransferase II deficiencyPaul J Isackson
Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14209, USA
Mol Genet Metab 89:323-31. 2006..The implications of these mutations are described in light of recent advances in our understanding of the molecular structure of members of the carnitine acyltransferase family...
- Lethal neonatal and severe late infantile forms of carnitine palmitoyltransferase II deficiency associated with compound heterozygosity for different protein truncation mutationsGeorgirene D Vladutiu
Division of Genetics, Children s Hospital of Buffalo and Department of Pediatrics, School of Medicine and Biomedical Sciences, University at Buffalo, New York 14209, USA
J Pediatr 141:734-6. 2002..A new phenotype for a severe late infantile form of CPT II deficiency with hypoglycemia is associated with compound heterozygosity for the severe Q413fs mutation and a mild point mutation (P50H)...
- Phenotypic variability among first-degree relatives with carnitine palmitoyltransferase II deficiencyGeorgirene D Vladutiu
Departments of Pediatrics, Neurology, and Pathology, School of Medicine and Biomedical Sciences, State University of New York, 936 Delaware Avenue, Buffalo, New York 14209, USA
Muscle Nerve 26:492-8. 2002..Reliance on carbohydrates during stress and hormonal alterations may explain, in part, the variance in ages of onset and serverity of symptoms in myopathic patients...
- Addition of quantitative 3-hydroxy-octadecanoic acid to the stable isotope gas chromatography-mass spectrometry method for measuring 3-hydroxy fatty acidsPatricia M Jones
University of Texas Southwestern Medical Center, Department of Pathology, and Children s Medical Center of Dallas, Dallas, TX 75235, USA
Clin Chem 48:176-9. 2002
- Establishing a reference interval for measurement of flux through the mitochondrial fatty acid oxidation pathway in cultured skin fibroblastsSrinivas B Narayan
Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Clin Chem 51:644-6. 2005
- Bile acylcarnitine profiles in pediatric liver disease do not interfere with the diagnosis of long-chain fatty acid oxidation defectsFranklin Fuda
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, and Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia, PA 19104 4399, United States
Clin Chim Acta 367:185-8. 2006..Disorders of fatty acid oxidation frequently present with deranged liver function and the effect of hepatic disease on biliary acylcarnitine excretion are unknown...
- Reye-like syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenaseMichael J Bennett
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
Mol Genet Metab 89:74-9. 2006..The spectrum of M/SCHAD phenotype should be broadened to include acute liver disease...
- Medium-chain fatty acids undergo elongation before beta-oxidation in fibroblastsPatricia M Jones
Department of Pathology, University of Texas Southwestern Medical Center, Dalls, TX 75235, USA
Biochem Biophys Res Commun 346:193-7. 2006..This previously undescribed metabolic step may have important implications for the metabolism of medium-chain triglycerides, components in the dietary treatment of a number of disorders...
- Molecular assay for detection of the common carnitine palmitoyltransferase 1A 1436(C>T) mutationJason Y Park
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine and the Hospital of the University of Pennsylvania, Philadelphia, 19104, USA
Clin Chem Lab Med 44:1090-1. 2006..The present study offers a molecular method for assessing CPT1A 1436 (C>T) mutation status...
- Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: implications for cryotherapy and lipid raft functionDinesh Rakheja
Department of Pathology, MC 9073, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
Med Hypotheses 65:1120-3. 2005..Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment...
- CLN3P, the Batten's disease protein, is a novel palmitoyl-protein Delta-9 desaturaseSrinivas B Narayan
Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Ann Neurol 60:570-7. 2006..Although the gene for the disorder was cloned more than a decade ago, the function of the encoded protein, CLN3P, has not been defined thus far...
- Assays of fatty acid beta-oxidation activityMichael J Bennett
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Metabolic Disease Laboratory, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Methods Cell Biol 80:179-97. 2007
- Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) micePrem S Shekhawat
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
Mol Genet Metab 92:315-24. 2007..Our studies suggest that carnitine supplementation, as a means of boosting fatty acid oxidation, may be therapeutically beneficial in patients with inflammation of the intestinal tract...
- Hyperinsulinism in infancy and childhood: when an insulin level is not always enoughAndrew A Palladino
The Children s Hospital of Philadelphia, Division of Endocrinology, Philadelphia, PA, USA
Clin Chem 54:256-63. 2008..HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders...
- The mitochondrial inner membrane protein mitofilin controls cristae morphologyGeorge B John
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Mol Biol Cell 16:1543-54. 2005..We propose that mitofilin is a critical organizer of the mitochondrial cristae morphology and thus indispensable for normal mitochondrial function...
- The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitusBrian N Finck
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 109:121-30. 2002....
- Carnitine content and expression of mitochondrial beta-oxidation enzymes in placentas of wild-type (OCTN2(+/+)) and OCTN2 Null (OCTN2(-/-)) MicePrem S Shekhawat
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
Pediatr Res 56:323-8. 2004....
- Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseasesPrem Shekhawat
Departments of Pediatric, Washington University School of Medicine, St Louis, Missouri 63110, USA
Am J Physiol Endocrinol Metab 284:E1098-105. 2003..Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy...
- Effect of L-carnitine supplementation on cardiac carnitine palmitoyltransferase activities and plasma carnitine concentrations in adriamycin-treated ratsHye Ran Yoon
Metabolic Disease Detection Laboratory, Seoul Medical Science Institute, Korea
Pediatr Res 53:788-92. 2003..05). This study supports the concept that ADR toxicity results from the inhibition of both CPT I and CPT II activities and that one of the causes of ADR-induced cardiomyopathy is a result of globally impaired fatty acid oxidation...
- Accumulation of 3-hydroxy-fatty acids in the culture medium of long-chain L-3-hydroxyacyl CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein-deficient skin fibroblasts: implications for medium chain triglyceride dietary treatment of LCHAD dPatricia M Jones
Department of Pathology, University of Texas, Southwestern Medical Center, Dallas 75235, USA
Pediatr Res 53:783-7. 2003..Our results suggest that a medium-chain triglyceride preparation that is higher in decanoate may be more effective in reducing the accumulation of potentially toxic long-chain 3-hydroxy-fatty acids in LCHAD deficiency...
- Absence of the G1528C (E474Q) mutation in the alpha-subunit of the mitochondrial trifunctional protein in women with acute fatty liver of pregnancyAnibran Maitra
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Pediatr Res 51:658-61. 2002..It is likely that AFLP arising in the context of fetal LCHAD deficiency represents only one of the possible etiologies for this uncommon disorder, and the metabolic basis of AFLP is more heterogeneous than previously believed...
- Carnitine palmitoyltransferase II deficiency: a clinical, biochemical, and molecular reviewEllen Sigauke
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Lab Invest 83:1543-54. 2003..We review the clinical features, the diagnostic protocol including expanded neonatal screening, the treatment, and the biochemical and molecular basis of CPT II deficiency...
- General mitochondrial trifunctional protein (TFP) deficiency as a result of either alpha- or beta-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnoverUte Spiekerkoetter
Department of Pediatrics and Vanderbilt Children s Hospital, Nashville, TN 37232, USA
Pediatr Res 55:190-6. 2004..Both alpha- and beta-subunit mutations result in TFP complex instability, demonstrating that the mechanism of disease is the same in alpha- or beta-mutation-derived disease and explaining the biochemical and clinical similarities...
- Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in deficiency of the mitochondrial trifunctional proteinUte Spiekerkoetter
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Muscle Nerve 29:66-72. 2004..Therefore, this disorder must be considered in the differential diagnosis of progressive peripheral neuropathy with or without episodic myoglobinuria...
- Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficienciesSusan R Hintz
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University, Palo Alto, California 94304, USA
Mol Genet Metab 75:120-7. 2002..However, timely analysis and reporting of results to clinicians are essential, because these disorders can manifest in the first few days of life...
- Cloning and characterization of the NAD-dependent 7alpha-Hydroxysteroid dehydrogenase from Bacteroides fragilisMichael J Bennett
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
Curr Microbiol 47:475-84. 2003..The predicted amino acid sequence of the ORF showed strong sequence similarity to three other bacterial 7-HSDHs, all in the short-chain dehydrogenase family. The regulation of expression of this gene is currently under investigation...
- CLN3P, the Batten disease protein, localizes to membrane lipid rafts (detergent-resistant membranes)Dinesh Rakheja
Department of Pathology, Children s Medical Center of Dallas and the University of Texas Southwestern Medical Center, Dallas, TX, USA
Biochem Biophys Res Commun 317:988-91. 2004..In this study, we demonstrate that CLN3P resides on membrane lipid raft domains (detergent-resistant membranes) and provide important new data towards possible functions of the protein...
- Fatty acid oxidation disordersPiero Rinaldo
Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Biochemical Genetics Laboratory, Rochester, Minnesota 55905, USA
Annu Rev Physiol 64:477-502. 2002..This review addresses the normal process of mitochondrial fatty acid beta-oxidation and discusses the clinical, metabolic, and molecular aspects of more than 20 known inherited diseases of this pathway that have been described to date...
- CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiencyPaul J Isackson
Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, SUNY at Buffalo, 100 High Street, Buffalo, NY 14203, USA
Mol Genet Metab 94:422-7. 2008..In addition, based on currently available structural, biochemical and clinical data, we have classified all 64 known disease-causing mutations into groups with different predicted phenotypes depending on their CPT2 allelic counterparts...