title: Diagnostic Algorithm for Glycogenoses and Myoadenylate Deaminase Deficiency Based on Exercise Testing Parameters: A Prospective Study.
abstract: OBJECTIVE
  Our aim was to evaluate the accuracy of aerobic exercise testing to diagnose metabolic myopathies.
  
  
  METHODS
  From December 2008 to September 2012, all the consecutive patients that underwent both metabolic exercise testing and a muscle biopsy were prospectively enrolled. Subjects performed an incremental and maximal exercise testing on a cycle ergometer. Lactate, pyruvate, and ammonia concentrations were determined from venous blood samples drawn at rest, during exercise (50% predicted maximal power, peak exercise), and recovery (2, 5, 10, and 15 min). Biopsies from vastus lateralis or deltoid muscles were analysed using standard techniques (reference test). Myoadenylate deaminase (MAD) activity was determined using p-nitro blue tetrazolium staining in muscle cryostat sections. Glycogen storage was assessed using periodic acid-Schiff staining. The diagnostic accuracy of plasma metabolite levels to identify absent and decreased MAD activity was assessed using Receiver Operating Characteristic (ROC) curve analysis.
  
  
  RESULTS
  The study involved 51 patients. Omitting patients with glycogenoses (n = 3), MAD staining was absent in 5, decreased in 6, and normal in 37 subjects. Lactate/pyruvate at the 10th minute of recovery provided the greatest area under the ROC curves (AUC, 0.893 ± 0.067) to differentiate Abnormal from Normal MAD activity. The lactate/rest ratio at the 10th minute of recovery from exercise displayed the best AUC (1.0) for discriminating between Decreased and Absent MAD activities. The resulting decision tree achieved a diagnostic accuracy of 86.3%.
  
  
  CONCLUSIONS
  The present algorithm provides a non-invasive test to accurately predict absent and decreased MAD activity, facilitating the selection of patients for muscle biopsy and target appropriate histochemical analysis.
authors.affiliation: Physiology Department-EA 1274, CHRU Cavale Blanche, Brest, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Rannou
authors.affiliation: Pathology Department, CHRU Morvan, Brest, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Uguen
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1078, Brest, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Scotet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1078, Brest, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Maréchal
authors.affiliation: Biochemistry Department, Robert Debré Hospital-APHP, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Rigal
authors.affiliation: Pathology Department-EA 4685 LNB, CHRU Morvan, Brest, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.affiliation: Pathology Department, CHRU Morvan, Brest, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Gobin
authors.affiliation: Biochemistry Department, CHRU Cavale Blanche, Brest, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Carré
authors.affiliation: Neurology Department-EA 4685 LNB, Clermont-Tonnerre Armed Forces Hospital, Brest, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zagnoli
authors.affiliation: Physiology Department-EA 1274, CHRU Cavale Blanche, Brest, France.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Giroux-Metges
mesh_terms: D000659:AMP Deaminase / Q000172:deficiency* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001706:Biopsy; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D006008:Glycogen Storage Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D000659:AMP Deaminase