Globoid Cell Leukodystrophy

Globoid Cell Leukodystrophy

Globoid Cell Leukodystrophy, also known as Krabbe's Disease, is a genetically inherited condition belonging to a category known as "storage diseases." A storage disease occurs when a particular enzyme, which is necessary for a normal process within the body, is deficient, and as a result, the compound which the enzyme normally acts upon builds up. This build-up leads to the expression of the disease and its symptoms, typically not at birth, but generally at a consistent age for each specific storage disease.

In the case of Globoid Cell Leukodystrophy, the deficient enzyme is galactocerebroside beta-galactosidase. This enzyme normally is involved in the breakdown of fats in the brain and spinal cord. When it is deficient, the compound galactocerebroside begins to build up. Galactocerebroside is a component of myelin, which is the fatty substance that surrounds and insulates nerve cells, keeping the electrical impulses properly isolated within the cells. When Galactocerebroside builds up, the production of myelin is affected, and as a result, there is a progressive loss of the myelin sheath on nerve cells in the brain and spinal cord.

Age of Onset
Puppies affected with Globoid Cell Leukodystrophy are normal at birth, but they may begin showing symptoms as early as four weeks or as late as six months. Basset Hounds are the exception, since they may not show symptoms for several years.

Symptoms of Globoid Cell Leukodystrophy
Symptoms are typically progressive (gradually worsening) and include stiffness when walking, weakness, lack of balance and coordination, tremors, loss of control (especially of hindquarters), and typically will eventually progress to paralysis and possible blindness. As would be expected, there are also generally behavioral changes that occur in conjunction with the physiological symptoms.

Breeds Affected
Globoid Cell Leukodystrophy is most often seen in the Cairn Terrier and West Highland White Terrier (Westie). Less commonly affected are Basset Hound, Miniature Poodle, Blue Tick Coonhound, Pomeranian, Beagle, Dalmatian, and Irish Setter.

How Globoid Cell Leukodystrophy Is Inherited
Globoid Cell Leukodystrophy is known to be an autosomal recessive genetic disorder in Cairns and West Highland White Terriers. It is not currently known if the mode of inheritance is the same in other breeds. "Autosomal" simply means that the condition is caused by a gene on a non-sex chromosome, so the condition is not linked to sex, and the fact that it is a recessive condition means that a dog must have a pair of affected genes, one from each parent, in order to express the disease. If a dog has only one affected gene and one normal gene, it will not be considered affected by Globoid Cell Leukodystrophy, but will be considered a carrier, capable of producing affected offspring if mated with another carrier or with an affected dog.

However, Globoid Cell Leukodystrophy is a bit unusual in that even carriers do exhibit measurable physiologic signs of abnormality. Dogs that are affected with GCL, having both affected genes, will have a measurable galactocerebroside beta-galactosidase activity that is about 18% of normal. Carriers, though, don't have 100% normal activity levels; theirs measures about 50% on average.

Diagnosis
Preliminary diagnosis is typically based on the progression of symptoms, along with diagnostic testing that rules out other more common conditions with similar symptoms. A blood test is now available, through Jefferson Medical College in Pennsylvania, that evaluates enzyme activity. Not only can this test be helpful in diagnosing affected dogs, but it can also help identify carriers so that they can be removed from any breeding program.

Treatment
Unfortunately, there is no treatment for Globoid Cell Leukodystrophy. It is invariably fatal.