Null mutations and lethal congenital form of glycogen storage disease type IV

Stefania Assereto, Otto P. van Diggelen, Luisa Diogo, Eva Morava, Denise Cassandrini, Isabel Carreira, Willem Pieter de Boode, Jildau Dilling, Paula Garcia, Margarida Henriques, Olinda Rebelo, Henk ter Laak, Carlo Minetti, Claudio Bruno

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Glycogen branching enzyme deficiency (glycogen storage disease type IV, GSD-IV) is a rare autosomal recessive disorder of the glycogen synthesis with high mortality. Two female newborns showed severe hypotonia at birth and both died of cardiorespiratory failure, at 4 and 12 weeks, respectively. In both patients, muscle biopsies showed deposits of PAS-positive diastase-resistant material and biochemical analysis in cultured fibroblasts showed markedly reduced glycogen branching enzyme activity. Direct sequencing of GBE1 gene revealed that patient 1 was homozygous for a novel c.691 + 5 g > c in intron 5 (IVS5 + 5 g > c). RT-PCR analysis of GBE1 transcripts from fibroblasts cDNA showed that this mutation produce aberrant splicing. Patient 2 was homozygous for a novel c.1643G > A mutation leading to a stop at codon 548 in exon 13 (p.W548X). These data underscore that in GSD-IV a severe phenotype correlates with null mutations, and indicate that RNA analysis is necessary to characterize functional consequences of intronic mutations.

Original languageEnglish (US)
Pages (from-to)445-450
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Sep 21 2007


  • GBE1 gene
  • Glycogen branching enzyme deficiency
  • Glycogen storage disease type IV
  • Polyglucosan body

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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