Lysosomal disease due to a defect in α-N-acetylglucosaminidase (NAGLU), with heparan sulfate accumulation and predominantly neurological involvement. It causes progressive degeneration of the CNS in young dogs, with subtle visceral and skeletal signs. The canine form in the Schipperke is a natural model of human Sanfilippo B syndrome and has been used in preclinical trials of intrathecal gene therapy.

Characterized breed: Schipperke. Study of 3219 genotyped dogs (2003-2019): 1.5 % affected homozygotes, 23.6 % clinically healthy heterozygous carriers and 74.9 % normal homozygotes. Frequencies decreased after genetic screening of the breed.

- Progressive neurological deterioration in the young animal\n- Ataxia and tremor\n- Behavioural changes\n- Seizures\n- Impaired response to commands\n- Mild or late visceral signs

Canine MPS IIIB was characterized in the Schipperke. Raj, Ellinwood and Giger (2020) sequenced the six exons of NAGLU in three affected and six healthy dogs and identified the causal insertion (poly-A tail of 40-70 bp plus an 11-bp duplication in exon 6). Between 2003 and 2019 they genotyped 3219 Schipperkes: 1.5 % affected homozygotes, 23.6 % healthy carriers and 74.9 % normal homozygotes. The canine model has been used in preclinical trials of CNS gene therapy.

- Genotype breeders before mating\n- Do not cross two carriers: 25 % risk of affected homozygotes\n- A carrier may be crossed with a clear dog; offspring intended for breeding must be tested\n- Exclude affected homozygotes from breeding\n- After a confirmed case, do not repeat the parental mating and inform the buyer of the status

Differential diagnosis with other MPS (IIIA and VII), with other degenerative encephalopathies of the young dog and with toxins. Enzyme assay in leukocytes/tissue and molecular study confirm. The predominantly neurological presentation with little somatic involvement points towards MPS III.

1. Raj K et al. 2020. An exonic insertion in the NAGLU gene causing Mucopolysaccharidosis IIIB in Schipperke dogs. Sci Rep 10:3170. PMID: 32081995
2. OMIA:001342-9615 - Mucopolysaccharidosis IIIB. https://omia.org/OMIA001342/9615/