title: Novel mutations in the gene encoding acid α-1,4-glucosidase in a patient with late-onset glycogen storage disease type II (Pompe disease) with impaired intelligence.
abstract: A 17-year-old Japanese man was referred to our hospital because of highly elevated serum levels of creatine kinase (CK) and transaminases. On admission, the proximal muscles of the lower extremities were found to be predominantly affected, and a score of 3/5 was obtained on Medical Research Council (MRC) scale. Muscular atrophy was evident and Gowers' sign was positive. His functional vital capacity (FVC) was markedly reduced. The results of the third edition of the Wechsler Adult Intelligence Scale (WAIS-III) indicated impairment of the patient's intelligence. Muscle biopsy showed scattered intracytoplasmic vacuoles with basophilic amorphous materials inside which were strongly stained by both periodic acid Schiff (PAS) and acid phosphatase. Biochemical analysis of the muscle tissue confirmed the diagnosis of GSDII because the glucosidase activity was 1.0 nmol/4 MU/mg/30 min (control range, 7.3 ± 2.2). Genetic analysis revealed a novel compound heterozygous missense mutation in GAA--c.1814 G >A (p.Gly605Asp) and c.1846 G >A (p.Asp616Asn) both in exon 13.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Japan. tmuraoka@med.kagawa-u.ac.jp
authors.forename: Tomie
authors.initials: T
authors.lastname: Muraoka
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Hitomi
authors.initials: H
authors.lastname: Imachi
authors.forename: Fumi
authors.initials: F
authors.lastname: Kikuchi
authors.forename: Takuo
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Iwama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Tokiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Sugie
authors.forename: Kaori
authors.initials: K
authors.lastname: Adachi
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005087:Glucan 1,4-alpha-Glucosidase / Q000235:genetics*; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000201:enzymology / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D020125:Mutation, Missense; D017386:Sequence Homology, Amino Acid
chemical_list: D005087:Glucan 1,4-alpha-Glucosidase