title: PFKM gene defect and glycogen storage disease GSDVII with misleading enzyme histochemistry.
abstract: OBJECTIVE
  To elaborate the diagnostic methods used as "gold standard" in one of the most common glycogen storage diseases (GSDs), Tarui disease (GSDVII).
  
  
  METHODS
  Two siblings with disease suggestive of GSD underwent thorough clinical analysis, including muscle biopsy, muscle MRI, exercise tests, laboratory examinations, and whole-exome sequencing (WES).
  
  
  RESULTS
  Both siblings had juvenile-onset exercise intolerance with cramping and infrequent myoglobinuria. Muscle biopsy showed extralysosomal glycogen accumulation, but because of normal phosphofructokinase histochemistry, GSDVII was thought to be excluded. However, WES revealed a causative homozygous PFKM gene defect, R39Q, in both siblings, establishing the diagnosis of GSDVII, which was confirmed by very low residual phosphofructo-1-kinase (PFK) enzyme activity in biochemical studies.
  
  
  CONCLUSIONS
  We suggest that in patients with suspicion of GSD and extralysosomal glycogen accumulation, biochemical activity assay of PFK followed by molecular genetics should be performed even when enzyme histochemistry is normal.
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Auranen
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Palmio
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Emil
authors.initials: E
authors.lastname: Ylikallio
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Huovinen
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Sandell
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Viitaniemi
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Piirilä
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Tyynismaa
authors.affiliation: Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd