Diagnosis of type 1B and 1C glycogen storage disease

Classical type la glycogen storage disease (McKusick 23220) is a severe metabolic disorder caused by a deficiency of the catalytic subunit of the hepatic microsomal glucose-6-phosphatase enzyme. However, it has recently been determined that at least five different polypeptides are required for normal glucose-6-phosphatase activity in vivo (reviewed by Burchell, 1990). The catalytic subunit of the glucose-6-phosphatase enzyme is situated with its active site in the lumen of the endoplasmic reticulum and it is associated with a regulatory Ca 2 + binding protein. In addition, three transport proteins, termed T1, Tz and T 3 respectively, allow the substrates and products glucose-6-phosphate, phosphate (and pyrophosphate) and glucose to cross the endoplasmic reticulum membrane. Another genetic deficiency, type lb glycogen storage disease (McKusick 23222), with similar clinical features to classical type la glycogen storage disease, has been recognized for some time, in which glucose-6phosphatase is abnormal in intact microsomes and in vivo, but normal in disrupted microsomes. The first reports of a specific defect in such patients were of a defect in the transport protein T 1 (e.g. Narisawa et al., 1978; Lange et al., 1980). Since then most cases with abnormal glucose-6-phosphatase activity in intact microsomes and normal activity in disrupted microsomes have been assumed to be type lb glycogen storage disease without the assays having been carried out which would detect deficiencies in T 2 or T3, type lc and type ld glycogen storage disease respectively.