title: A novel mutation of the GAA gene in a Finnish late-onset Pompe disease patient: clinical phenotype and follow-up with enzyme replacement therapy.
abstract: Pompe disease is a rare, progressive disease leading to skeletal muscle weakness due to deficiency of the acid alpha-glucosidase (GAA) enzyme. Herein we report the first diagnosed Finnish patient with a phenotype compatible with the late-onset form of Pompe disease. Molecular genetic analysis of the GAA gene revealed a novel missense mutation, 1725C>A (Y575X), combined with a previously reported mutation, 1634C>T (P545L). Human recombinant alpha-glucosidase enzyme (alglucosidase-alpha) treatment was initiated for this patient at age 20 years. After 12 months she was no longer fully wheelchair-bound, and muscle strength had improved. No disease progression was visible on muscle magnetic resonance imaging of the lower limbs, and the energy state of the muscle cells increased by 46% on phosphorus magnetic resonance spectroscopy. Overall, our findings suggest that enzyme replacement therapy is indicated, even in patients with late-onset Pompe disease, to halt disease progression and improve the quality of daily life.
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, P.O. Box 340, Helsinki 00029, Finland. marinposti@hotmial.com
authors.forename: Mari P
authors.initials: MP
authors.lastname: Korpela
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.forename: Mervi I
authors.initials: MI
authors.lastname: Löfberg
authors.forename: Marjut H
authors.initials: MH
authors.lastname: Timonen
authors.forename: Antti E
authors.initials: AE
authors.lastname: Lamminen
authors.forename: Sari M K
authors.initials: SM
authors.lastname: Kiuru-Enari
mesh_terms: D004252:DNA Mutational Analysis; D004562:Electrocardiography; D004576:Electromyography / Q000379:methods; D004583:Electrons; D005260:Female; D005387:Finland / Q000208:ethnology; D005500:Follow-Up Studies; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000627:therapeutic use; D014443:Tyrosine / Q000235:genetics; D055815:Young Adult; D000520:alpha-Glucosidases / Q000235:genetics* / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D014443:Tyrosine; D000520:alpha-Glucosidases