The molecular background of glycogen metabolism disorders

The molecular pathology of classical glycogen storage disorders, glycogen s ynthase deficiency and Fanconi-Bickel syndrome is reviewed. The isolation o f the respective cDNAs, the chromosomal localization of the genes and the e lucidation of the genomic organization enabled mutation analysis in most di sorders. The findings have shed light on the multi-protein structure of the glucose-6-phosphatase system, the phosphorylase kinase enzymatic complex a nd the molecular background of the differential tissue expression in debran ching enzyme deficiency. The immediate practical benefit of these studies i s our extending ability to predict the outcome of clinical variants and to offer genetic counseling to most families. The elucidation of the tertiary structure of these proteins and their structure-function relationship poses major challenges for the future.