title: Fatal infantile neuromuscular presentation of glycogen storage disease type IV.
abstract: Glycogen storage disease type IV or Andersen disease is an autosomal recessive disorder due to deficiency of glycogen branching enzyme. Typically, glycogen storage disease type IV presents with rapidly progressive liver cirrhosis and death in childhood. Variants include a cardiopathic form of childhood, a relatively benign myopathic form of young adults, and a late-onset neurodegenerative disorder (adult polyglucosan body disease). A severe neuromuscular variant resembling Werdnig-Hoffmann disease has also been described in two patients. The objective was to describe two additional infants with the neuromuscular variant and novel mutations in the GBE1 gene. Branching enzyme assay, Western blot, RT-PCR and sequencing were performed in muscle biopsies from both patients. The cDNA of patient 1 was subcloned and sequenced to define the mutations. Muscle biopsies showed accumulation of periodic acid Schiff-positive, diastase-resistant storage material in both patients and increased lysosomal enzyme activity in patient 1. Branching enzyme activity in muscle was negligible in both patients, and Western blot showed decreased branching enzyme protein. Patient 1 had two single base pair deletions, one in exon 10 (1238delT) and the other in exon 12 (1467delC), and each parent was heterozygous for one of the deletions. Patient 2 had a large homozygous deletion that spanned 627 bp and included exons 8-12. Patient 1, who died at 41 days, had neurophysiological and neuropathological features of Spinal Muscular Atrophy. Patient 2, who died at 5(1/2) weeks, had a predominantly myopathic process. The infantile neuromuscular form of glycogen storage disease type IV is considered extremely rare, but our encountering two patients in close succession suggests that the disease may be underdiagnosed.
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, 4-420, 630 West 168th Street, New York, NY 10032, USA.
authors.forename: Stacey K H
authors.initials: SK
authors.lastname: Tay
authors.forename: Hasan O
authors.initials: HO
authors.lastname: Akman
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Michael G
authors.initials: MG
authors.lastname: Pike
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Hays
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Valberg
authors.forename: James R
authors.initials: JR
authors.lastname: Mickelson
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D015061:1,4-alpha-Glucan Branching Enzyme / Q000378:metabolism; D010131:Aminosalicylic Acid / Q000378:metabolism; D001706:Biopsy / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001933:Brain Stem / Q000201:enzymology / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005260:Female; D006011:Glycogen Storage Disease Type IV / Q000150:complications / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D019746:Intramolecular Oxidoreductases; D008247:Lysosomes / Q000201:enzymology; D008854:Microscopy, Electron / Q000379:methods; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009154:Mutation; D009468:Neuromuscular Diseases / Q000201:enzymology / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014897:Spinal Muscular Atrophies of Childhood / Q000150:complications / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D015534:Trans-Activators; D010131:Aminosalicylic Acid; D015061:1,4-alpha-Glucan Branching Enzyme; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases