title: Branching enzyme deficiency: expanding the clinical spectrum.
abstract: OBJECTIVE
  The neuromuscular presentation of glycogen branching enzyme deficiency includes a severe infantile form and a late-onset variant known as adult polyglucosan body disease. Herein, we describe 2 patients with adult acute onset of fluctuating neurological signs and brain magnetic resonance imaging lesions simulating multiple sclerosis. A better definition of this new clinical entity is needed to facilitate diagnosis.
  
  
  OBJECTIVE
  To describe the clinical presentation and progression of a new intermediate variant of glycogen branching enzyme deficiency and to discuss genotype-phenotype correlations.
  
  
  METHODS
  Clinical, biochemical, morphological, and molecular study of 2 patients followed up for 6 years and 8 years at academic medical centers. The participants were 2 patients of non-Ashkenazi descent with adult acute onset of neurological signs initially diagnosed as multiple sclerosis.
  
  
  METHODS
  Clinical course, muscle and nerve morphology, longitudinal study of brain magnetic resonance imaging, and glycogen branching enzyme activity and GBE1 molecular analysis.
  
  
  RESULTS
  Molecular analysis showed that one patient was homozygous (c.1544G>A) and the other patient was compound heterozygous (c.1544G>A and c.1961-1962delCA) for GBE1 mutations. Residual glycogen branching enzyme activity was 16% and 30% of normal in leukocytes. Both patients manifested acute episodes of transient neurological symptoms, and neurological impairment was mild at age 45 years and 53 years. Brain magnetic resonance imaging revealed nonprogressive white matter lesions and spinocerebellar atrophy similar to typical adult polyglucosan body disease.
  
  
  CONCLUSIONS
  GBE1 mutations can cause an early adult-onset relapsing-remitting form of polyglucosan body disease distinct from adult polyglucosan body disease in several ways, including younger age at onset, history of infantile liver involvement, and subacute and remitting course simulating multiple sclerosis. This should orient neurologists toward the correct diagnosis.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York2Unidad de Enfermedades Neuromusculares, Servicio de Neurología, Hospital Universitario Virgen del Rocío, Instituto de Biomédicina de Sevilla, Consejo Superior de Investigación.
authors.forename: Carmen
authors.initials: C
authors.lastname: Paradas
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Hasan O
authors.initials: HO
authors.lastname: Akman
authors.affiliation: Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ionete
authors.affiliation: Rusk Institute of Rehabilitation, NYU Langone Medical Center, New York, New York.
authors.forename: Heather
authors.initials: H
authors.lastname: Lau
authors.affiliation: Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Riskind
authors.affiliation: Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester.
authors.forename: David E
authors.initials: DE
authors.lastname: Jones
authors.affiliation: Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Smith
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
mesh_terms: D000208:Acute Disease; D017668:Age of Onset; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006011:Glycogen Storage Disease Type IV / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
chemical_list: D006004:Glycogen Debranching Enzyme System; C577876:GBE1 protein, human