title: New cases of adult-onset Sandhoff disease with a cerebellar or lower motor neuron phenotype.
abstract: Sandhoff disease is a lipid-storage disorder caused by a defect in ganglioside metabolism. It is caused by a lack of functional N-acetyl-beta-d-glucosaminidase A and B due to mutations in the HEXB gene. Typical, early-onset Sandhoff disease presents before 9 months of age with progressive psychomotor retardation and early death. A late-onset form of Sandhoff disease is rare, and its symptoms are heterogeneous. As drug trials that aim to intervene in the disease mechanism are emerging, the recognition and identification of Sandhoff disease patients-particularly those with atypical phenotypes-are becoming more important. The authors describe six new late-onset Sandhoff cases demonstrating cerebellar ataxia or lower motor neuron (LMN) involvement combined with, mostly subclinical, neuropathy. Two different mutations were found: IVS 12-26 G/A and c.1514G-->A. In patients with either progressive cerebellar ataxia or LMN disease in the setting of a possibly recessive disorder, Sandhoff disease should be suspected, even when the onset age is over 45 years.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Neurology (935), Nijmegen 6500 HB, The Netherlands.
authors.forename: C C S
authors.initials: CC
authors.lastname: Delnooz
authors.forename: D J
authors.initials: DJ
authors.lastname: Lefeber
authors.forename: S M C
authors.initials: SM
authors.lastname: Langemeijer
authors.forename: S
authors.initials: S
authors.lastname: Hoffjan
authors.forename: G
authors.initials: G
authors.lastname: Dekomien
authors.forename: M J
authors.initials: MJ
authors.lastname: Zwarts
authors.forename: B G M
authors.initials: BG
authors.lastname: Van Engelen
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: H J
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: B P C
authors.initials: BP
authors.lastname: van de Warrenburg
mesh_terms: D000118:Acetylglucosaminidase / Q000097:blood; D000328:Adult; D017668:Age of Onset; D002524:Cerebellar Ataxia / Q000150:complications*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications*; D009154:Mutation; D010641:Phenotype; D012497:Sandhoff Disease / Q000097:blood / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D054821:beta-Hexosaminidase beta Chain / Q000235:genetics
chemical_list: D000118:Acetylglucosaminidase; C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain