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Mucopolysaccharidosis IIIa Dachshund Type (MPS IIIA)
| Acronym: | MPS IIIA |
| Gene: | SGSH |
| Mutation: | c.740_742delCCA |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Mucopolysaccharidosis IIIa Dachshund Type (MPS IIIA) is a hereditary lysosomal storage disorder affecting the Dachshund breeds, such as Longhaired, Shorthaired, Miniature, Standard, Wirehaired Dachshund, etc. It 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 Dachshund Type (MPS IIIA) is the first animal homolog of the human Sanfilippo syndrome type. 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. As the first symptom, pelvic limb ataxia is observed by the owners at age of 3 years. The pelvic limb ataxia is characterized by hypermetric dysmetria and frequent stumbling and falling. After noticing the first symptoms, neurologic signs progress, and the dog’s whole body starts swaying from side to side in a standing position and a head tremor is evident on movement initiation. The dog becomes unable to climb stairs and falling is frequent. Blood examination reveals abnormal levels of oxalate crystalluria in the affected dog. No behavioral changes have been observed.
Histologic examination reveals lesions in the spinal cord, brainstem, and cerebellar neuronal degeneration. Within neurons, accumulated lips are detected. Extreme amounts of membrane-bound intracytoplasmic vacuoles were found within hepatocytes, renal tubular epithelial cells, and dermal fibroblasts. The disorder is progressive, but although its progression is slow, affected dogs are usually euthanized within a few years of diagnosis. Mucopolysaccharidosis IIIa Dachshund 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:
Arnovich EL, Carmichael KP, Morizono H, Koutlas IG, Deanching M, Hoganson G, Fischer A, Whitley CB. Canine heparin sulfate sulfamidase and the molecular pathology underlying Sanfilippo syndrome type A in Dachshunds. Genomics. 2000 Aug 15; 68(1):80-4.
Fischer A, Carmichael KP, Munnell JF, Jhabvala P, Thompson JN, Matalon R, Jezyk PF, Wang P, Giger U. Sulfamidase deficiency in a family of Dachshunds: A canine model of mucopolysaccharidosis IIIA (Sanfilippo A). Pediatr Res. 1998 July;44(1):74–82.