Lysosomal storage diseases

What is ... ?: 

The lysosomal storage diseases include ceroid lipofuscinosis, fucosidosis, glucocerebrosidosis, glycogen storage disease type III, GM1 gangliosidosis, GM2 gangliosidosis, mucopolysaccharidosis I, sphingomyelinosis. In these disorders, there is a deficiency of a particular enzyme necessary for normal metabolic processes within the body. The result is an accumulation in cells ("storage") of whatever product the enzyme normally acts upon. Cells become swollen and incapable of normal function. Although these conditions can affect many different body systems, most often the clinical signs relate to abnormalities in the nervous system. Typically, animals with a storage disease are normal at birth, fail to grow as rapidly as littermates, and at a consistent age, develop progressive signs of a nervous disorder which will ultimately prove fatal.

These disorders are generally rare. Because of similar diseases in people however, these conditions are better studied than many other, more common, inherited disorders in dogs.

Abnormality Breeds affected (RARE) Special tests Clinical features
Ceroid lipofuscinosis (Batten disease) many breeds - Australian cattle dog, border collie, chihuahua, cocker spaniel, dalmatian, wire-haired dachshund, English setter, Tibetan terrier none, diagnosis confirmed on post-mortem signs usually start around 1 to 2 years of age, vary between breeds (see resources below), may include diminished eyesight, abnormal behaviour, incoordination, seizures
Fucosidosis English springer spaniel measure enzyme levels signs by 6 to 12 months, include slow learning, anxiety and behaviour changes, which gradually progress over the next 18 months or so, to severe incoordination, dementia, visual problems 
Glucocerebrosidosis (Gaucher's disease) Australian silky terrier measure enzyme levels signs by 4 to 8 months, include incoordination, tremors, hyperactivity, stiff gait
Glycogen storage disease type III (Cori's disease) Akita, German shepherd measure enzyme levels signs by 6 to 12 weeks, muscle tremors, incoordination, hypoglycemia (low blood sugar), seizures, death by 8 months
GM1 gangliosidosis Portuguese water dog, English springer spaniel measure enzyme levels signs by 2 to 4 months, include vision problems, lethargy, difficulty in walking, death occurs by 8 months.
GM2 gangliosidosis (type B - Tay-Sachs disease, type O - Sandhoff's disease) German short-haired pointer (rare) measure enzyme levels signs by 6 to 9 months, include visual problems, abnormal behavior, incoordination, stiff gait
Mucopolysaccharidosis I Plott hound (rare) measure enzyme levels signs often develop later, in adulthood; this is a connective tissue disorder and signs include musculoskeletal abnormalities, and heart disease due to thickened valves.
Sphingomyelinosis (Niemann-Pick disease) very rare measure enzyme levels signs by 2 to 5 months, include incoordination, exaggerated gait, dullness

 

For the veterinarian: More detailed information on the pathophysiology of these conditions, the specific molecular defects, and the clinical differences between breeds is available in the resources listed below. The first also describes diagnostic tests available and pending.

 

 

See also: 
Globoid cell leukodystrophy (galactocerebrosidosis)
How is ... inherited?: 

Where inheritance has been determined, it is autosomal recessive.

What does ... mean to your dog & you?: 

 These disorders, fortunately rare, are devastating. Pups are normal at birth and then gradually (most commonly before 1 year of age) develop signs of neurologic disease. Their demeanor, behaviour and motor abilities are affected to varying degrees depending on the disorder, but the condition always worsens until the dog dies or is euthanized, usually within 6 months of the first signs.

How is ... diagnosed?: 

 These conditions are difficult to diagnose, both because they are very uncommon and because the clinical signs are often vague (eg.depression, behaviour change). Generally the routine diagnostic tests your veterinarian will carry out will show no abnormalities.
 
Once a lysosomal storage disease is suspected, your veterinarian will submit a blood sample for specific diagnostic tests which are now available for many of these disorders. These tests measure blood levels of the particular enzyme involved, and many can detect carriers of the disorder (who have about 50 per cent normal enzyme levels) as well as affected dogs. For those disorders in which the specific genetic defect has been identified, it is likely that before long there will be a DNA test that can be used to differentiate normal, carrier, and affected dogs.
 

How is ... treated?: 

 Unfortunately there is no treatment available for these disorders, which can only be controlled by good breeding programmes.
 
As gene therapies emerge, they will likely first be developed for these conditions, many of which are controlled by a single gene and involve a single defective enzyme.
 

For the veterinarian: 

 Generally there is a combination of cerebral and cerebellar signs.

Breeding advice: 

 Affected animals and their parents (carriers of the defective gene) should not be bred. Siblings are suspect carriers and should only be used for breeding if a screening test has been carried out, showing that they are not carriers. In this way, these devastating diseases can be greatly reduced or eliminated from the breeds in which they occur.
 
FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.
 

Resources: 

 Ackerman, L. 1999. The Genetic Condition: A Guide to Health Problems in Purebred Dogs. pp 103-107. AAHA Press. Lakewood, Colorado.

 March, P.A. 1996. Degenerative brain disease. Vet. Clin. of N.A.  Small Animal Practice. 26(4): 945-971.


What breeds are affected by ... ?
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