In other species: emu , dog , pig

Categories: Lysosomal storage disease

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 252920 (trait) , 609701 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: Also known as Sanfilippo syndrome type B

Inheritance: Karageorgos et al. (2007): "All affected animals were derived from a 'closed herd' into which no new genetic material had been brought for approximately 30 years. ... The herd consisted of 1300 breeder cows and bulls were used at 3%. Bulls were used for four seasons; hence there was ample scope for inbreeding to occur. Under these breeding conditions about 4–5 clinically affected animals were observed each year ... ." Breed information was kindly provided by L. Taylor.

Molecular basis: In what must be a sign of the times, Karageorgos et al. (2007) documented the first reported occurrence of this disorder in cattle and, in the same paper, also reported its molecular basis; in this case a missense mutation E452K (c.1354G>A) in the gene for alpha-N-acetylglucosaminidase (NAGLU).

Clinical features: Karageorgos et al. 2007: "No clinical signs were observed at weaning (6–8 monthsof age). Clinical signs develop progressively over the lifespan of affected cattle and include: hairy ears and longer muzzle hairs; bigger-boned head; loss of herding instinct, aimless wandering and tendency to stand alone; growth to a smaller stature, 85% of normal height; progressive loss of alertness ... ; development of cautious behaviour around objects like yarding gates, but not blindness as judged by avoidance of obstacles in their path; and becoming very placid and sedate in nature. Clinical signs are usually evident in affected animals atapproximately 2 years of age, but can be observed at 12 months at the very earliest. Animals live to approximately 3–5 years in a paddock situation ... . When caredfor in a less hazardous environment they will live for 5–6 years but eventually show progressive ataxia and stumbling gait (affecting fore and hind limbs), swaying of the hind quarters and loss of body condition, and become emaciated and die."

Pathology: Karageorgos et al. 2007: The "missense mutation resulted in only 1.5% of normal NAGLU activity. ... Histopathology and electron microscopy revealed widespread neuronal lesions, vacuolated hepatocytes and apparent ganglioside accumulation as indicated by membranous whorls ... . The tissues most severely affected included the liver, kidney and central nervous system ... ."

Breed: Santa Gertrudis (Cattle) (VBO_0000368).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: