title: Carnitine-acylcarnitine translocase deficiency: Two neonatal cases with common splicing mutation and in vitro bezafibrate response.
abstract: BACKGROUND
  Mitochondrial fatty acid oxidation (FAO) disorders are among the causes of acute encephalopathy- or myopathy-like illness. Carnitine-acylcarnitine translocase (CACT) deficiency is a rare FAO disorder, which represent an energy production insufficiency during prolonged fasting, febrile illness, or increased muscular activity. CACT deficiency is caused by mutations of the SLC25A20 gene. Most patients developed severe metabolic decompensation in the neonatal period and died in infancy despite aggressive treatment.
  
  
  METHODS
  We herein report the clinical findings of two unrelated cases of CACT deficiency with mutation confirmation, and in vitro bezafibrate responses using in vitro probe acylcarnitine (IVP) assay. Patients 1 and 2 are products of nonconsanguineous parents. Both patients developed cardiac arrest at day 3 of life but survived the initial events. Their blood chemistry revealed hypoglycemia and metabolic acidosis. The acylcarnitine profiles in both patients demonstrated increased long-chain acylcarnitines, suggesting CACT or carnitine palmitoyltransferase-2 (CPT2) deficiency.
  
  
  RESULTS
  The mutation analysis identified homozygous IVS2-10T>G in the SLC25A20 gene in both patients, confirming the diagnosis of CACT deficiency. The IVP assay revealed increased C16, C16:1, but decreased C2 with improvement by bezafibrate in the cultured fibroblasts. The short-term clinical trial of bezafibrate in Patient 1 did not show clinical improvement, and died after starting the trial for 6 months.
  
  
  CONCLUSIONS
  This splicing mutation has been identified in other Asian populations indicating a possible founder effect. IVP assay of cultured fibroblasts could determine a response to bezafibrate treatment. A long-term clinical trial of more enrolled patients is required for evaluation of this therapy.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: nithiwat_v@hotmail.com.
authors.forename: Nithiwat
authors.initials: N
authors.lastname: Vatanavicharn
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Medical Information Sciences Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.affiliation: Division of Nutrition, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Narumon
authors.initials: N
authors.lastname: Densupsoontorn
authors.affiliation: Division of Nutrition, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pipop
authors.initials: P
authors.lastname: Jirapinyo
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Achara
authors.initials: A
authors.lastname: Sathienkijkanchai
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pornswan
authors.initials: P
authors.lastname: Wasant
mesh_terms: D001629:Bezafibrate / Q000494:pharmacology* / Q000627:therapeutic use; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002333:Carnitine Acyltransferases / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005804:Genes, Lethal; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D016896:Treatment Outcome
chemical_list: D000960:Hypolipidemic Agents; D026901:Membrane Transport Proteins; C116917:acylcarnitine; C120109:SLC25A20 protein, human; D002333:Carnitine Acyltransferases; D002331:Carnitine; D001629:Bezafibrate
keywords: Bezafibrate; CACT deficiency; IVP assay; SLC25A20 mutation