ABSTRACT
The classic form of glycogen storage disease originally described by von Gierke [1] is caused by a deficiency of glucose-6-phosphatase (Fig 60.1). It became apparent that there were subtypes of glycogenosis I and a considerably expanded glucose-6-phosphatase system when patients were studied who appeared to have von Gierke disease in which glucose6-phosphatase activity in frozen liver was normal. The term glycogenosis type Ib was derived to distinguish these patients from those (Ia) in whom the activity of the enzyme is deficient
[2,3]. Narisawa and colleagues in 1978 [3] found defective glucose-6-phosphatase activity in fresh liver and restored activity by adding detergents; they suggested that the defect was in glucose-6-phosphate transport. The translocase defect was reported in 1980 by Lange and colleagues [4]. Type Ic was recognized [5] on the basis of normal activity of glucose6-phosphatase in detergent-disrupted microsomes, while activity in intact microsomes is defective for both glucose-6phosphate and carbamylphosphate substrates. Type Id with defective microsomal transport of glucose has not yet been observed clinically [6]. A variant of type Ia is a result of the
Glycogen Phosphate
Glucose-1-phosphate
Glucose-6-phosphate Glucose-6-phosphatase
Lactate
Hexokinase Glucose Glucose
Phosphorylase Debrancher
deficiency of the regulatory protein, designated Iasp, for stabilizing protein which has so far been reported in a single patient [7]; it is impossible to distinguish this from deficiency of the catalytic subunit clinically, and difficult biochemically unless the entire stabilizing protein is missing.
