Type VI Glycogen Storage Disease

Synonyms:
Liver Phosphorylase Deficiency, Hers Disease

In Type VI Glycogen Storage Disease (GSD VI), the most frequent first symptoms include an enlarged liver and low blood sugar (hypoglycemia). After we eat, excess glucose is stored as glycogen mostly in the liver to be used later when we are fasting (not eating for 3-4 hours) to maintain normal glucose levels in our body. The phosphorylase enzyme plays a vital role in the breakdown of glycogen into glucose.

Clinical Features:
Clinically, this form of glycogen storage disease appears to be similar to, but is usually considerably milder than glucose-6-phosphatase deficiency GSD (Type I GSD) since glucose can be made from protein. These patients present with hepatomegaly (liver enlargement) and growth retardation early in childhood. Since people with Type VI GSD are able to store glucose as glycogen but not able to release it normally, with time the stores of glycogen build up in the liver causing the liver to swell (hepatomegaly). This is much like being able to place groceries from the store into your kitchen cabinets, but not being able to get the food out of the cabinets when needed. Hypoglycemia (low blood sugars) and elevated ketone concentrations in the blood and urine after a period of fasting are the hallmarks of these disorders. Hyperlipidemia (elevated cholesterol and fats in the blood) and abnormalities in the liver function tests are usually mild if present. Lactic acid and uric acid are normal. The heart and skeletal muscles are not involved. The hepatomegaly improves with good metabolic control. Hepatic adenomas are rare in well treated individuals with GSD VI, and liver failure does not occur.

Diagnosis:
The diagnosis of this disease can be made by genetic testing from DNA extracted from blood or saliva. Liver biopsies to measure phosphorylase activity, which is reduced in this disease, are not necessary in most cases and not recommended if Type VI GSD is suspected.

Treatment:
Treatment with cornstarch and a high protein diet is recommended in an effort to achieve normal labs and normal growth. Treatment improves growth velocity and bone density in this condition, and reduces the frequency of hypoglycemia and ketosis. Treatment is individualized in an attempt to maintain glucose concentrations above 70 mg/dL and normalize ketones after an overnight fast.

Links

Hers Disease from National Organization for Rare Disorders [NORD]

Type VI info on Online Mendelian Inheritance in Man searchable database [OMIM]

GSD Type VI from GeneReviews

Type VI GSD info from eMedicine/Medscape