Purpose: Glycogen storage disease type IV (GSD IV) has historically been divided into discrete hepatic (classic hepatic, non-progressive hepatic) and neuromuscular (perinatal-congenital neuromuscular, juvenile neuromuscular) subtypes. However, the extent to which this subtype-based classification system accurately captures the landscape of phenotypic variation among GSD IV patients has not been systematically assessed.Methods: This study synthesized clinical data from all eligible cases of GSD IV in the published literature to evaluate whether this disorder is better conceptualized as discrete subtypes or a clinical continuum. A novel phenotypic scoring approach was applied to characterize the extent of hepatic, neuromuscular, and cardiac involvement in each eligible patient.Results: 146 patients met all inclusion criteria. The majority (61%) of those with sufficient data to be scored exhibited phenotypes that were not fully consistent with any of the established subtypes. These included patients who exhibited combined hepatic-neuromuscular involvement; patients whose phenotypes were intermediate between the established hepatic or neuromuscular subtypes; and patients who presented with predominantly cardiac disease.Conclusion: The application of this novel phenotypic scoring approach showed that–in contrast to the traditional subtype-based view–GSD IV may be better conceptualized as a multidimensional clinical continuum, whereby hepatic, neuromuscular, and cardiac involvement occur to varying degrees in different patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.