title: The effect of homozygous deletion of the BBOX1 and Fibin genes on carnitine level and acyl carnitine profile.
abstract: BACKGROUND
  Carnitine is a key molecule in energy metabolism that helps transport activated fatty acids into the mitochondria. Its homeostasis is achieved through oral intake, renal reabsorption and de novo biosynthesis. Unlike dietary intake and renal reabsorption, the importance of de novo biosynthesis pathway in carnitine homeostasis remains unclear, due to lack of animal models and description of a single patient defective in this pathway.
  
  
  METHODS
  We identified by array comparative genomic hybridization a 42 months-old girl homozygote for a 221 Kb interstitial deletions at 11p14.2, that overlaps the genes encoding Fibin and butyrobetaine-gamma 2-oxoglutarate dioxygenase 1 (BBOX1), an enzyme essential for the biosynthesis of carnitine de novo. She presented microcephaly, speech delay, growth retardation and minor facial anomalies. The levels of almost all evaluated metabolites were normal. Her serum level of free carnitine was at the lower limit of the reference range, while her acylcarnitine to free carnitine ratio was normal.
  
  
  CONCLUSIONS
  We present an individual with a completely defective carnitine de novo biosynthesis. This condition results in mildly decreased free carnitine level, but not in clinical manifestations characteristic of carnitine deficiency disorders, suggesting that dietary carnitine intake and renal reabsorption are sufficient to carnitine homeostasis. Our results also demonstrate that haploinsufficiency of BBOX1 and/or Fibin is not associated with Primrose syndrome as previously suggested.
authors.forename: Ali
authors.initials: A
authors.lastname: Rashidi-Nezhad
authors.forename: Saeed
authors.initials: S
authors.lastname: Talebi
authors.forename: Homeira
authors.initials: H
authors.lastname: Saebnouri
authors.affiliation: Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. akramism@tums.ac.ir.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Akrami
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
mesh_terms: D000015:Abnormalities, Multiple / Q000473:pathology; D002114:Calcinosis / Q000473:pathology; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization; D004427:Ear Diseases / Q000473:pathology; D005260:Female; D015894:Genome, Human; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D009133:Muscular Atrophy / Q000473:pathology; D050563:gamma-Butyrobetaine Dioxygenase / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C116274:FIBP protein, human; D008565:Membrane Proteins; D050563:gamma-Butyrobetaine Dioxygenase; D002331:Carnitine