glyconstoragedisease

GLYCOGEN STORAGE DISEASE IN DOGS

Glycogen storage disease also known as glycogenosis is a rare inherited disorder centered in the liver and is characterised by deficient or defective activity of the enzymes responsible for metabolizing glycogen. There are various types of glycogen storage diseases, all of which lead to the accumulation of glycogen. Glycogen is the main carbohydrate storage material in the body which aids short term energy storage in cells by converting to glucose as the body needs it for metabolic requirements. The effect is hypoglycaemia because the affected individual is unable to mobilise glucose from glycogen stores. In other words Glycogen Storage Disease is the inability to break down glycogen, which is the form of sugar stored in the body. Because of the missing /impaired enzyme, the body cannot create glucose from glycogen and it is difficult to maintain normal blood sugar levels between meals without constant feedings. This abnormal accumulation of glycogen in the tissues can result in the enlargement and dysfunction of various organs, including the liver, heart, and kidneys.

Glucose is required as an obligatory energy source for the normal function of the following tissues :
Blood cells Renal medullary cells Nervous tissue (especially the brain) Fast-twitch muscle fibres use glucose as an energy source. These are the predominant fibres in fast sped

There are four different types of glycogen storage diseases in the dog:

   1. Type 1 (von Gierke's Disease) due to deficiency of glucose-6-phosphatase. Occurs in 6-12 week old puppies resulting in slow growth, hypoglycaemia, hepatomegaly (due excess glycogen) and decreased response to glucagon. Laboratory diagnosis : increased blood concentrations of lactate, uric acid, cholesterol, free fatty acids, and triglycerides. von Gierke's Disease primarily found in Maltese puppies, may result in failure to thrive, mental depression, low blood sugar (a condition known as hypoglycemia), and eventually death (or, to avoid symptoms, euthanasia) by sixty days of age.

   2. Type II - (Pompe's disease). Caused by deficiency of lysosomal acid alpha-glucosidase. Causes excessive glycogen build-up in cardiac and skeletal muscle. This disease has been reported in mainly male Lapland dogs. Signs occur after 6 months of age and include vomiting, regurgitation, megaoesophagus, panting, muscle weakness, abnormal cardiac function. The disease is slowly progressive and affected dogs die or are euthanased by 18 months of age.

   3. Type III - Functional (so called hunting-dog) hypoglycaemia. Similar to Cori's disease in humans which is caused by a deficiency of amylo-t-phosphatase. This condition affects hyperactive working dogs after 1-2 hours of exercise. They recover after a few minutes of rest, but remain exhausted. This disease may not in fact be a glycogen-storage disease - it could be related to poor nutritional management and stress factors, including psychological, physical and environmental factors (eg high temperatures). Feeding during exercise may prevent the condition from occurring.  Type III, Cori’s disease, is usually found in young female German Shepherds, results in depression, weakness, failure to grow. Hepatomegaly and mild hypoglycemia develop in animals with this disease.

   4. Type IV Generalised - Caused by a deficiency of phosphofructokinase. Results in hemolytic anemia, a condition in which red blood cells are destroyed, and hemoglobinuria, a condition in which the protein hemoglobin (which helps transport oxygen throughout the body) is abnormally highly concentrated in the patient’s urine. Affects small breed puppies and juveniles and has been found in English Spring Spaniels aged two to nine. This may be a stress-related hypoglycaemia precipitated by cold, excitement or starvation - and as yet it is not proved to be a true glycogen-storage disease.

Diagnostic procedures vary depending on the symptoms and type of glycogen storage disease suspected. A tissue enzyme analysis and determination of glycogen levels can serve as a definitive diagnosis. Other tests may include urine analysis, genetic testing, and electrocardiography (ECG) to check the electrical output from the heart for changes.

A dog that presents with suspected glycogen storage disease will need to be continuously monitored and treated for hypoglycemia. Treatment will vary depending on the type of glycogen storage disease diagnosed and the severity of the symptoms. The main objective of treatment is to control hypoglycemia.  Types I and Types III in dogs may require the administration of intravenous (IV) dextrose in order to manage an immediate crisis of dangerously low blood sugar. Unfortunately, long-term management of this condition is futile. Related hypoglycemia may also be regulated with diet, by feeding frequent (every one-three hours) portions of a high-carbohydrate/low fat diet. Most animals with glycogenosis are euthanized due to the progressive deterioration of their physical health.

Animals that develop glycogen storage disease should not be bred, nor should the parents of such animals be bred out again, in order to avoid the possibility of future cases.

The clinical signs of hypoglycaemia include :
Muscle weakness Exercise intolerance Fatigue Collapse Ataxia	CNS depression (dazed) Muscle twitches (fasciculations) Hyperexcitation Convulsions Coma