title: Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: Review of 15 years Experience.
abstract: BACKGROUND
  The treatment of long-chain mitochondrial β-oxidation disorders (LC-FOD) with a low fat-high carbohydrate diet, a diet rich in medium-even-chain triglycerides (MCT), or a combination of both has been associated with high morbidity and mortality for decades. The pathological tableau appears to be caused by energy deficiency resulting from reduced availability of citric acid cycle (CAC) intermediates required for optimal oxidation of acetyl-CoA. This hypothesis was investigated by diet therapy with carnitine and anaplerotic triheptanoin (TH).
  
  
  METHODS
  Fifty-two documented LC-FOD patients were studied in this investigation (age range: birth to 51 years). Safety monitoring included serial quantitative measurements of routine blood chemistries, blood levels of carnitine and acylcarnitines, and urinary organic acids.
  
  
  RESULTS
  The average frequency of serious clinical complications were reduced from ~60% with conventional diet therapy to 10% with TH and carnitine treatment and mortality decreased from ~65% with conventional diet therapy to 3.8%. Carnitine supplementation was uncomplicated.
  
  
  CONCLUSIONS
  The energy deficiency in LC-FOD patients was corrected safely and more effectively with the triheptanoin diet and carnitine supplement than with conventional diet therapy. Safe intervention in neonates and infants will permit earlier intervention following pre-natal diagnosis or diagnosis by expanded newborn screening.
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA; Investigations were performed at the Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX, USA. Electronic address: chasroe@earthlink.net.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Roe
authors.affiliation: Departments of Nutrition and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Henri
authors.initials: H
authors.lastname: Brunengraber
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D019343:Citric Acid / Q000652:urine; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019344:Lactic Acid / Q000652:urine; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy* / Q000401:mortality; D008293:Malates / Q000652:urine; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy* / Q000401:mortality; D010084:Oxidation-Reduction; D019802:Succinic Acid / Q000652:urine; D016019:Survival Analysis; D016896:Treatment Outcome; D014280:Triglycerides / Q000627:therapeutic use*
chemical_list: D005227:Fatty Acids; D008293:Malates; D014280:Triglycerides; C116917:acylcarnitine; D019343:Citric Acid; C531010:triheptanoin; D019344:Lactic Acid; C030298:malic acid; D019802:Succinic Acid; D002331:Carnitine
keywords: Anaplerosis; Fat oxidation disorders; Ketogenic diet therapy; Triheptanoin