title: A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction.
abstract: BACKGROUND
  Congenital generalized lipodystrophy (CGL) results from mutations in AGPAT2, encoding 1-acyl-glycerol-3-phosphate-acyltransferase 2 (CGL1; MIM 608594), BSCL2, encoding seipin (CGL2; MIM 269700), CAV1, encoding caveolin1 (CGL3; MIM 612526) or PTRF, encoding polymerase I and transcript release factor (CGL4; MIM 613327). This study aims to investigate the genotype/phenotype relationship and search for a possible pathogenic mechanism in a patient with CGL.
  
  
  METHODS
  Case report.
  
  
  METHODS
  A 7-day-old child of consanguineous Turkish parents presented with a generalized loss of subcutaneous fat. He had a strikingly enlarged liver, high serum triglycerides, and hyperglycaemia, suggestive for CGL.
  
  
  RESULTS
  A novel homozygous mutation in the acceptor splice site of exon 5 of the BSCL2 gene was found in the genome of the proband. This mutation causes a complex RNA splicing defect and results in two different aberrant seipin proteins, which were normally expressed and localized to the endoplasmic reticulum like wild type protein. Analysis of the patient's urine showed intermittent elevations of citric acid intermediates and persistently high concentrations of ethylmalonic acid, suggestive of a disturbance of the mitochondrial respiratory chain.
  
  
  CONCLUSIONS
  Here we report abnormal urinary organic acid levels, indicative of mitochondrial dysfunction, in a patient with CGL resulting from a novel mutation in BSCL2. Our findings suggest for the first time an association between CGL and secondary mitochondrial dysfunction.
authors: Department of Metabolic Diseases, UMC Utrecht, Room KE.03.139.2, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.
authors: Ellen H
authors: EH
authors: Jeninga
authors: Monique
authors: M
authors: de Vroede
authors: Nicole
authors: N
authors: Hamers
authors: Johannes M P J
authors: JM
authors: Breur
authors: Nanda M
authors: NM
authors: Verhoeven-Duif
authors: Ruud
authors: R
authors: Berger
authors: Eric
authors: E
authors: Kalkhoven