GM2 Gangliosidosis (Sandhoff disease)

 

Gene: HEXB

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.

Mutations:

Korat mutation: Deletion, HEXB gene; c.39 del, p.(L14S fs STOP 82)

Domestic shorthair mutation: Inversion, HEXB gene; c.1467_1491 inv, p.(F489L fs STOP 4)

Japanese domestic mutation: Substitution, HEXB gene; c.667 C>T, p.(R223 STOP)

Burmese mutation: Deletion, HEXB gene; c.1244-8_1250 del.15pb, exon12

Medical system: Neurological

Breeds: Asian, Burmese, Burmilla, Domestic Cat, Domestic Shorthair, Korat

Age of onset of symptoms: 2 months of age

GM2 gangliosidosis (or Sandhoff Disease) is a fatal neurodegenerative disease caused by a lack of hexosaminidase, an enzyme found in lysosomes within the cells.  Clinical signs appear around 2 months of age and include neurological symptoms such as tremors that affect the head and the hind limbs.  Growth is impaired.  The disease is similar to GM1 gangliosidosis but with a faster clinical progression.  The treatment is symptomatic with an aim to relieve the animal’s suffering.

 

References:

OMIA link: [1462-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Bradbury AM, Morrison NE, Hwang M, et al. (2009) Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab. 97(1):53-59. [pubmed/19231264]

Muldoon LL, Neuwelt EA, Pagel MA, Weiss DL. (1994) Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease). Am J Pathol. 144(5):1109-18. [pubmed/8178934]