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Mucopolysaccharidosis IIIa New Zealand Huntaway Type
| Acronym: | MPS IIIA |
| Gene: | SGSH |
| Mutation: | c.685_686insA |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
| Method: |
Genetics and characteristics
Mucopolysaccharidosis IIIa New Zealand Huntaway Type (MPS IIIA) is a hereditary lysosomal storage disorder affecting New Zealand Huntaway breed. The disorder is a part of a bigger group of disorders, mucopolysaccharidoses. Until now, eleven types of mucopolysaccharidosis have been differentiated in humans. They vary in clinical symptoms, but some characteristics are common to all forms, such as dwarfism, undeveloped epiphyseal centers, dysostosis multiplex, facial dysmorphia, corneal clouding, and organomegaly. They are known to affect humans, mice, dogs, and cats. Mucopolysaccharidosis III, also known as Sanfilippo syndrome, comes in two different forms, Mucopolysaccharidosis IIIa and Mucopolysaccharidosis IIIb. Mucopolysaccharidosis IIIa New Zealand Huntaway Type (MPS IIIA) is an animal homolog of human Sanfilippo syndrome type and it is characterized by progressive neurological signs with little effect on bones and other organs as occurs in other forms of mucopolysaccharides.
Enzyme heparan sulfate sulfamidase (HSS), also known as heparan N-sulfatase, is an exohydrolase active inside the lysosomes, where it catalyzes the cleavage of the N-sulfate bond within the heparan sulfate. When the enzyme is present in too low concentrations, or its activity is not proper, accumulation of heparan sulfate in tissues occurs, resulting in the development of symptoms of Sanfilippo syndrome type A. In humans, accumulation of heparan sulfate in a proteoglycan form is associated also with other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. The age of onset of Mucopolysaccharidosis IIIa in affected New Zealand Huntaway dogs is around 1.5 years of age. Symptoms include progressive ataxia, high stepping, prancing gait affecting the forelegs, and difficulty with jumping. Ataxia and hypermetria are present in all four limbs. A crossed exterior response is seen when the hindlimb withdrawal reflexes are being assessed. The patella, cranial tibial, and gastrocnemius reflexes are exaggerated in both hindlimbs with clonus observed on the right side. Behavioral abnormalities have been observed, such as loss of learned behavior. Due to the rapid progression of the disease, affected dogs are often euthanized within a month of the onset of clinical signs.
Mucopolysaccharidosis IIIa New Zealand Huntaway Type (MPS IIIA) is caused by a mutation within the SGSH gene. The disorder is inherited as an autosomal recessive trait. A dog can be clear, carrier, or affected. Healthy parents of an affected dog are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Jolly RD, Johnstone AC, Hubbard DE et al. Screening for the mucopolysaccharidosis-IIIA gene in Huntaway dogs. New Zealand Vet J. 2002;50(3):122.
Yogalingam G, Pollard T, Gliddon B et al. Identification of a mutation causing mucopolysaccharidosis type IIA in New Zealand Huntaway dogs. Genomics. 2002 Feb;79(2):150-153.