Neuropediatrics 2006; 37 - MP74
DOI: 10.1055/s-2006-943671

MYOPATHIC FORM OF VERY-LONG CHAIN ACYL-COA DEHYDROGENASE (VLCAD) DEFICIENCY DIAGNOSED BY BIOCHEMICAL AND GENETIC ANALYSIS FROM DRIED BLOOD SPOT. IDENTIFICATION OF TWO NOVEL MUTATIONS

C Bruno 1, S Scapolan 1, D Cassandrini 1, M Cassanello 2, M Pedemonte 1, L Bergamino 1, A Simoni 3, U Caruso 2, C Minetti 1
  • 1Neuromuscular Disease Unit
  • 2Laboratory of Metabolic Diseases, G. Gaslini Institute, Genova, Italy
  • 3Ospedale di Carpi (MO), Italy

Objectives: To describe a girl identified by tandem mass spectrometry (MS/MS) of blood spot acylcarnitines, and confirmed by molecular analysis, to have the myopathic form of very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency.

Methods: A 9-year-old girl presented with exercise-related episodes of myalgia and myoglobinuria, with elevated creatine kinase (CK) levels, since 6 years of age. Resting CK was normal. Neuromuscular examination and routinary laboratory investigations were unremarkable. Electromyography revealed a myopathic pattern. Acylcarnitines profile was determined by tandem mass spectrometry of dried blood spot and genetic analysis of the ACADVL gene was performed on DNA extracted from blood spot.

Results: Increased C14 acylcarnitine were suggestive of VLCAD deficiency, and molecular analysis revealed two novel heterozygous mutations, an inframe 3-bp deletion in exon 15 and a missense mutation in exon 19. Both parents resulted to be asymptomatic carriers.

Conclusion: These data underline the possibility to perform a correct diagnosis throughout a biochemical and genetic analysis of dried blood spot in patients with metabolic myopathies characterized by exercise intolerance and myoglobinuria, thus avoiding muscle biopsy. In addition, this study further enlarges the list of mutations in the ACADVL gene, confirming that the myopathic form of VLCAD deficiency is associated with mild mutations.