title: Juvenile-onset motor neuron disease caused by novel mutations in β-hexosaminidase.
abstract: A 12 year-old female presented with a seven-year history of progressive muscle weakness, atrophy, tremor and fasciculations. Cognition was normal. Rectal biopsy revealed intracellular storage material and biochemical testing indicated low hexosaminidase activity consistent with juvenile-onset G(M2)-gangliosidosis. Genetic evaluation revealed compound heterozygosity with two novel mutations in the hexosaminidase β-subunit (c.512-3 C>A and c.1613+15_1613+18dup). Protein analysis was consistent with biochemical findings and indicated only a small portion of β-subunits were properly processed. These results provide additional insight into juvenile-onset G(M2)-gangliosidoses and further expand the number of β-hexosaminidase mutations associated with motor neuron disease.
authors.affiliation: Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. tyler.pierson@cshs.org
authors.forename: Tyler Mark
authors.initials: TM
authors.lastname: Pierson
authors.forename: Paola A
authors.initials: PA
authors.lastname: Torres
authors.forename: Bei-Jin
authors.initials: BJ
authors.lastname: Zeng
authors.forename: Allan M
authors.initials: AM
authors.lastname: Glanzman
authors.forename: David
authors.initials: D
authors.lastname: Adams
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finkel
authors.forename: Don J
authors.initials: DJ
authors.lastname: Mahuran
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.forename: Gihan I
authors.initials: GI
authors.lastname: Tennekoon
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Kolodny
mesh_terms: D017668:Age of Onset; D002648:Child; D005260:Female; D006801:Humans; D016472:Motor Neuron Disease / Q000235:genetics* / Q000523:psychology; D009154:Mutation; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D001619:beta-N-Acetylhexosaminidases