Genetic variants associated with inborn errors of carbohydrate metabolism in southwestern Colombia.

Inborn errors of carbohydrate metabolism (EIM) are the product of interruption of the catabolic or anabolic pathways of different carbohydrates, glucose, fructose, galactose and glycogen being the most common, and belong to a heterogeneous group of disorders that can be inherited. or be the result of spontaneous genetic variants. Currently, the information on these pathologies in Colombia is scarce and there are no exact data on prevalence and incidence (1). With the objective of determining the genomic variants associated with inborn errors of carbohydrate metabolism in a population from southwestern Colombia without a clinical and/or paraclinical diagnosis of this group of diseases, a cross-sectional, descriptive, non-experimental study was carried out, with the results obtained from the sequencing of the complete exome of 320 patients with different pathologies, without clinical suspicion of EIM from carbohydrates. The variants found were classified according to the standards of the American College of Medical Genetics and genomics, using population databases and bioinformatic software to predict the clinical significance of the different variants. The allelic frequency of each variant was calculated and interaction networks were developed for each gene associated with carbohydrate EIM. As a result, 286 variants were found, of which 206 have not been previously reported in the literature, 73 variants of benign or probably benign significance, 6 variants of uncertain significance in the GALT, GAK1, ALDOB, GAA, and SLC2A1 genes, and 1 variant of pathogenic significance in the GALT gene associated with classic galactosemia. Common pseudodeficiency variants were identified; p.Val98Met, p.Asn156Asp, p.Asp91Asn, p.Gly576Ser, p.Thr927Ile; p.Asn156Asp being the one with the highest allelic frequency, 4.3%. The interaction networks of genes and molecules allowed us to discover associations between genes with shared ontological functions and close metabolic pathways. The findings described alert the medical community to establish early diagnosis programs. This will allow specific treatments, associated with a transdisciplinary management that minimizes the morbidity and mortality attributed to this disease, including adequate genetic counseling and education on the risk of heritability, carrying out anticipatory and preventive medicine and implementation of the expanded neonatal screening program for early identification. of these disorders, approaching precision medicine.

Bibliography

1. Jeanmonod R, Asuka E, Jeanmonod D. Inborn Errors Of Metabolism. In Treasure Island (FL); 2023.