Editorial: Inborn errors of carbohydrate metabolism volume II

Inherited disorders of carbohydrate metabolism comprise a heterogeneous and expanding group of rare disorders that disrupt fundamental cellular processes, including glycosylation, glycogen metabolism, and glucose transport. Although individually rare, collectively these disorders represent a clinically significant and often underrecognized burden of neurological, neuromuscular, ophthalmologic, and systemic manifestations. Advances in genomic technologies, disease modeling, and population-level analyses are now reshaping how these conditions are diagnosed, understood, and managed. This Research Topic represents Volume 2 of Inborn Errors of Carbohydrate Metabolism and builds directly upon the conceptual and clinical framework established in Volume 1, which surveyed major domains across congenital disorders of glycosylation (CDG), lysosomal storage diseases, glycogen storage disorders, and disorders of glucose and galactose metabolism, spanning molecular mechanisms, diagnostic strategies, and emerging therapies.The present volume focuses on phenotypic expansion, diagnostic pitfalls, tissuespecific disease mechanisms, and population-level impact, further illustrating the dynamic and evolving nature of this field. A recurring theme across the contributions is that genotype, biochemical defect, and clinical presentation do not always align in a predictable way, an issue that continues to challenge diagnosis, prognostication, and counseling. Several articles highlight that pathogenic variants in genes central to carbohydrate metabolism can present with a wide phenotypic spectrum, ranging from severe infantile encephalopathies to apparently asymptomatic adult presentations identified incidentally. These observations underscore the need for integrative diagnostic frameworks that extend beyond classical phenotype-based classifications. an embryo free of disease-causing alleles was selected for transfer and the pregnancy resulted in the birth of a healthy child. This case concretely illustrates how PGT-M can prevent recurrence of severe autosomal recessive lysosomal disease and reduce reliance on later prenatal decision points.Collectively, the articles in this Research Topic highlight several key directions for the field. First, phenotypic variability and incomplete penetrance are emerging as defining features rather than exceptions in disorders of carbohydrate metabolism. Second, early and accurate diagnosis-often reliant on subtle biochemical clues or broad genomic testing-is critical, particularly when disease-modifying therapies are available. Third, integrative approaches that combine clinical observation, functional modeling, and population-level data are essential for fully capturing disease mechanisms and impact.As therapeutic pipelines expand, the insights provided by these studies will be increasingly relevant for precision medicine. This Research Topic underscores that advancing the field will require not only identifying new disease-causing variants but also rethinking how we define disease onset, severity, and treatability across the lifespan.