The effect of homozygous deletion of the BBOX1 and Fibin genes on carnitine level and acyl carnitine profile
1 Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland
2 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina St, P.O. Box: 14155–6447, Tehran, Iran
3 Maternal, Fetal and Neonatal Research Center, Tehran University of Medical Sciences, Tehran, Iran
BMC Medical Genetics 2014, 15:75 doi:10.1186/1471-2350-15-75Published: 1 July 2014
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.
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.
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.