title: Clinical features and mutations in seven Chinese patients with very long chain acyl-CoA dehydrogenase deficiency.
abstract: BACKGROUND
  Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is an inherited metabolic disease caused by deleterious mutations in the ACADVL gene that encodes very long chain acyl-CoA dehydrogenase (VLCAD), and which can present as cardiomyopathy in neonates, as hypoketotic hypoglycemia in infancy, and as myopathy in late-onset patients. Although many ACADVL mutations have been described, no prevalent mutations in the ACADVL gene have been associated with VLCADD. Herein, we report the clinical course of the disease and explore the genetic mutation spectrum in seven Chinese patients with VLCADD.
  
  
  METHODS
  Seven Chinese patients, from newborn to 17 years old, were included in this study. Tandem mass spectrometry was performed to screen for VLCAD deficiency. All exons and flanking introns of the ACADVL gene were analyzed using polymerase chain reaction and direct sequencing. Online analysis tools were used to predict the impact of novel mutations.
  
  
  RESULTS
  All cases had elevated serum levels of tetradecanoylcarnitine (C14:1) which is the characteristic biomarker for VLCADD. The phenotype of VLCADD is heterogeneous. Two patients were hospitalized for hypoactivity and hypoglycemia shortly after birth. Three patients showed hepatomegaly and hypoglycemia in infancy. The other two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis. Three of the patients died at the age of 6-8 months. Eleven different mutations in the ACADVL gene in the 7 patients were identified, including seven reported mutations (p.S22X, p.W427X, p.A213T, p.G222R, p.R450H, c.296-297delCA, c.1605+1G>T) and four novel mutations (p.S72F, p.Q100X, p.M437T, p.D466Y). The p.R450H and p.D466Y (14.28%, 2/14 alleles) mutations were identified in two alleles respectively.
  
  
  CONCLUSIONS
  The clinical manifestations were heterog-eneous and ACADVL gene mutations were heterozygous in the seven VLCADD Chinese patients. R450H may be a relatively common mutation in Asian populations. The genotype and phenotype had a certain correlation in our patients.
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism and Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors.forename: Rui-Nan
authors.initials: RN
authors.lastname: Zhang
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Li
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Lian-Shu
authors.initials: LS
authors.lastname: Han
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Gu
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D000483:Alleles; D002648:Child; D002681:China / Q000453:epidemiology; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics* / Q000628:therapy; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D053719:Tandem Mass Spectrometry
chemical_list: D044942:Acyl-CoA Dehydrogenase, Long-Chain; C467805:ACADVL protein, human