Clinical Neuroscience

Atypical presentation of late-onset Sandhoff disease: a case report

SALAMON András 1, SZPISJAK László 1, ZÁDORI Dénes1, LÉNÁRT István2, MARÓTI Zoltán3, KALMÁR Tibor 3, BRIERLEY M. H. Charlotte4, DEEGAN B. Patrick 5, KLIVÉNYI Péter 1

NOVEMBER 30, 2021

Clinical Neuroscience - 2021;74(11-12)

DOI: https://doi.org/10.18071/isz.74.0425

Case Reports

Sandhoff disease is a rare type of hereditary (autosomal recessive) GM2-gangliosidosis, which is caused by mutation of the HEXB gene. Disruption of the β subunit of the hexosaminidase (Hex) enzyme affects the function of both the Hex-A and Hex-B isoforms. The severity and the age of onset of the disease (infantile or classic; juvenile; adult) depends on the residual activity of the enzyme. The late-onset form is characterized by diverse symptomatology, comprising motor neuron disease, ataxia, tremor, dystonia, psychiatric symptoms and neuropathy. A 36-year-old female patient has been presenting progressive, symmetrical lower limb weakness for 9 years. Detailed neurological examination revealed mild symmetrical weakness in the hip flexors without the involvement of other muscle groups. The patellar reflex was decreased on both sides. Laboratory tests showed no relevant alteration and routine electroencephalography and brain MRI were normal. Nerve conduction studies and electromyography revealed alterations corresponding to sensory neuropathy. Muscle biopsy demonstrated signs of mild neurogenic lesion. Her younger brother (32-year-old) was observed with similar symptoms. Detailed genetic study detected a known pathogenic missense mutation and a 15,088 base pair long known pathogenic deletion in the HEXB gene (NM_000521.4:c.1417G>A; NM_000521:c.-376-5836_669+1473del; double heterozygous state). Segregation analysis and hexosaminidase enzyme assay of the family further confirmed the diagnosis of late-onset Sandhoff disease. The purpose of this case report is to draw attention to the significance of late-onset Sandhoff disease amongst disorders presenting with proximal predominant symmetric lower limb muscle weakness in adulthood.

AFFILIATIONS

  1. Department of Neurology, University of Szeged, Szeged, Hungary
  2. Department of Pediatrics and Pediatric Health Center, University of Szeged, Szeged, Hungary
  3. Genetic Diagnostic Laboratory, Department of Pediatrics and Pediatric Health Center, University of Szeged, Szeged, Hungary
  4. Department of Neurology, Addenbrooke’s Hospital, Cambridge, United Kingdom
  5. Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom

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