Mucopolysaccharidosis IIIa Dachshund Type (MPS IIIA)
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 a first animal homolog of 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 is 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 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 the Alzheimer’s and the Parkinson’s disease.
Characteristics and Symptoms
As 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 first symptoms, neurologic signs progress, and dogs’ whole body starts swaying from side to side in standing position and a head tremor is evident on movement initiation. Dog becomes unable to climb stairs and falling is frequent. Blood examination reveals abnormal levels of oxalate crystalluria in affected dog. No behavioral changes have been observed.
Histologic examination reveals lesions in 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 SGSH gene. The disorder is inherited as an autosomal recessive trait. 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.
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.