Mucopolysaccharidosis

What is Mucopolysaccharidosis in dogs?

LysosomeMucopolysaccharidosis is an inherited Lysosomal Storage Disorder where affected dogs lack the adequate function of an enzyme called alpha-L-iduronidase. This enzyme is found in the lysosomes of the cells. The lysosomes are special storage areas or bags inside the cells of the body that contain a special mix of enzymes responsible for disassembling complex molecules in an orderly fashion when required. This order relies on each of the enzymes doing their bit at the right time. Dogs affected by Mucopolysaccharidosis are missing the alpha-L-iduronidase enzyme so are unable to fully complete the whole process of the molecule breakdown and as a result, are left with stores of half broken down molecules in the cells. These cells that contain these un-degraded molecules will either fail to function correctly or simply die leading to growth retardation and dysfunction of the major systems of the body, in particular the central nervous system.

Genetics of Mucopolysaccharidosis

Mucopolysaccharidosis is an autosomal recessive trait or disease, meaning that the effects of one faulty copy of the gene responsible will be cancelled out if the dog also has one normal copy. This means that if a dog has 2 faulty copies it will be affected by Mucopolysaccharidosis, one normal and one faulty makes the dog a carrier and two normal copies makes the dog clear for the condition. One of the genes that is mutated to cause Mucopolysaccharidosis is the IDUA gene responsible for the manufacture of the alpha-L-iduronidase enzyme.

What is the severity of Mucopolysaccharidosis?

Mucopolysaccharidosis is a very severe disease as it affects many of the affected dog’s cells leading to symptoms across the entire body with a high level of morbidity. Mucopolysaccharidosis leads to a very early death for affected dogs as there is no cure.

What are the symptoms of Mucopolysaccharidosis in dogs?

Dogs affected by Mucopolysaccharidosis can begin to show signs of the disease from about 4 to 6 months of age with the initial symptoms being delayed growth, skeletal deformities, pain and joint laxity. Depending on the particular mutation, different enzymes will be affected, so different parts of the body will have varying levels of impact. Some of the symptoms that an affected dog will show after the initial stage can include, tremors, balancing difficulties, trouble walking, joint dislocation, enlarged liver and tongue, eye cloudiness, arched back and a very stiff gait. Regardless of which body system is affected first or more greatly, Mucopolysaccharidosis is a progressive disease so the presenting symptoms will become worse with time.

Diagnosis of Mucopolysaccharidosis in dogs

Diagnosis of Mucopolysaccharidosis was only able to be made after a multiple of tests including physical examination, blood and urine testing and a complete biochemistry analysis to measure the lysosomal enzyme levels in the blood. Nowadays, a DNA Disease Screening test will give a very definitive answer as to whether Mucopolysaccharidosis is affecting the dog by looking at the genes responsible.

Treatment of Mucopolysaccharidosis in dogs

Bone marrow transplants in young and early stage dogs affected by Mucopolysaccharidosis have shown to give the affected dog a life that is near to being normal and enzyme replacement therapy can help. However, both are very expensive and in the case of bone marrow transplant, a suitable donor must also be found. Gene therapy may be a suitable treatment option in the future but is still being evaluated at this stage.

References

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Shull RM, Munger RJ, Spellacy E, Hall CW, Constantopoulos G, Neufeld EF. Canine alpha-L-iduronidase deficiency. A model of mucopolysaccharidosis I. Am J Pathol. 1982 Nov;109(2):244-8

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