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New cases of adult-onset Sandhoff disease with a cerebellar or lower motor neuron phenotype
  1. C C S Delnooz1,
  2. D J Lefeber2,
  3. S M C Langemeijer1,
  4. S Hoffjan3,
  5. G Dekomien3,
  6. M J Zwarts1,
  7. B G M Van Engelen1,
  8. R A Wevers2,
  9. H J Schelhaas1,
  10. B P C van de Warrenburg1
  1. 1Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  2. 2Laboratory of Pediatrics & Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  3. 3Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany
  1. Correspondence to Dr Bart P C van de Warrenburg, Radboud University Nijmegen Medical Centre, Department of Neurology (935), PO Box 9101, Nijmegen 6500 HB, The Netherlands; b.vandewarrenburg{at}neuro.umcn.nl

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-β-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.

  • Motor neuron disease (MND)
  • spinal muscular atrophy (SMA)
  • sandhoff disease
  • cerebellar ataxia
  • ganglioside

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Footnotes

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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