Liver glycogen storage diseases

Inherited deficiencies in specific enzymes of glycogen metabolism in both liver and muscle are the causes of glycogen storage diseases. 

There are important methodologic considerations which apply to the use of cultured amniotic fluid cells for the detection of biochemical disorders. The first is that the enzymes which can be sampled are those which are usually present in fibroblasts or fibroblast-like cells. Therefore, conditions such as phenylketonuria and glycogen storage disease type I, which are associated with deficiencies of enzymes present only in liver and kidney, are not amenable to this approach. The same also pertains to enzyme deficiencies affecting other specific tissues. 

The most common glycogen storage disease. Type I or von Gierke disease, is a deficiency in glucose 6-phosphatase in which glycogen structures are normal however, the liver is unable to dephosphory-late glucose 6-phosphate, and it remains trapped In the cell. 

However, in some glycogen storage diseases (see p. 128), the amount of glycogen in the liver and/or muscle can be significantly higher. 

The release of glucose from the glycogen stores in the liver is mediated by glucose 6-phosphatase, which is apparently embedded within the membranes of the endoplasmic reticulum. A labile enzyme, it consists of a 357-residue catalytic subrmit,251/252 which may be associated with other subunits that participate in transport.252 253 A deficiency of this enzyme causes the very severe type la glycogen storage disease (see Box 20-D).251 253 Only hepatocytes have significant glucose 6-phosphatase activity. 

Burchell, A. Glycogen storage diseases and the liver. Baill. Clin. Gastroenterol. 1998 12 337-353... 

Siciliano, M., de Candia, E., Ballarin, S., Vecchlo, FJM., Senidei, S., Annese, R., Landolfi, R., Rossi, L. Hepatocellular carcinoma complicating liver cirrhosis in type Ilia glycogen storage disease. X Chn. Gastroenterol. 2000 31 80-82... 

Individuals with a glucose-6-phosphatase (G-6-P —> Glucose, in the liver) deficiency develop a glycogen storage disease. This condition results in hypoglycemia, low blood sugar, accumulation of lactic acid and ketones. Distal kidney tubule excretion of uric acid is inhibited and hyperuricemia (XS uric acid) and gout results. 

Glycogen-storage disease samples data on normal, human-liver glycogen is not available. Calculated from C. L. and the -amylolysis or phosphorolysis limit (see Section IV). 

In the Type VI diseases, there appears to be abnormally low or complete absence of phosphorylase activity. In three cases (Type Via) examined by Hers, the activity of the liver phosphorylase was about 5 units, compared with values of 12-33 units for other cases of glycogen-storage disease, although the muscle phosphorylase activity was normal. 

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