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

Tomie Muraoka; Koji Murao; Hitomi Imachi; Fumi Kikuchi; Takuo Yoshimoto; Hisakazu Iwama; Hitoshi Hosokawa; Ichizo Nishino; Tokiko Fukuda; Hideo Sugie; Kaori Adachi; Eiji Nanba; Toshihiko Ishida

doi:10.2169/internalmedicine.50.5563

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

Intern Med. 2011;50(24):2987-91. doi: 10.2169/internalmedicine.50.5563. Epub 2011 Dec 15.

Authors

Tomie Muraoka¹, Koji Murao, Hitomi Imachi, Fumi Kikuchi, Takuo Yoshimoto, Hisakazu Iwama, Hitoshi Hosokawa, Ichizo Nishino, Tokiko Fukuda, Hideo Sugie, Kaori Adachi, Eiji Nanba, Toshihiko Ishida

Affiliation

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Japan. [email protected]

PMID: 22185990
DOI: 10.2169/internalmedicine.50.5563

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.

Publication types

Case Reports

MeSH terms

Adolescent
Age of Onset
Amino Acid Sequence
Amino Acid Substitution
Base Sequence
DNA Mutational Analysis
Glucan 1,4-alpha-Glucosidase / genetics*
Glycogen Storage Disease Type II / complications
Glycogen Storage Disease Type II / diagnosis
Glycogen Storage Disease Type II / enzymology*
Glycogen Storage Disease Type II / genetics*
Heterozygote
Humans
Intellectual Disability / complications
Intellectual Disability / enzymology
Intellectual Disability / genetics
Male
Molecular Sequence Data
Muscle, Skeletal / pathology
Mutation, Missense*
Sequence Homology, Amino Acid

Substances

Glucan 1,4-alpha-Glucosidase