Clinical, molecular and bioinformatic analysis a patient with Cori-Forbes disease in the Southwest of Colombia

Abstract

Introduction: Glycogen storage disease type III (GSDIII) or Cori Forbes disease is a disorder of the glycogenolysis process caused by variants of the AGL gene that encodes the glycogen debranching enzyme; It is located on chromosome 1p21.2 and its alteration generate an incomplete degradation of glycogen, leading to an accumulation of borderline dextrin in target organs, causing organomegaly and dysfunction. Objective: To characterize at the molecular level an elderly male lactating patient from southwestern Colombia with a clinical, biochemical diagnosis suspected of GSDIII. Materials and methods: An elderly male infant with a history of bronchopulmonary dysplasia, acute respiratory infection, gastroesophageal reflux, hepatomegaly, and lactose intolerance. A molecular study was performed by whole exome sequencing; the reported variants were evaluated by prediction software such as Mutation Taster, PROVEAN, UMD-Predictor, POLYPHEN, SIFT, Human Splicing Finder. Finally, a gene interaction network was performed using the GeneMania program to determine close gene associations. Results: 3 heterozygous variants located in the AGL gene were identified: p.Arg910 * that causes loss of the amyl-1,6 glucosidase domain and the glycogen-binding domain, and the variants p.Trp373Cys, p.Asn565 in the protein. The analysis of clinical significance by means of in-silico methods determined a pathogenic classification for all the variants. The interaction network will observe associations between the AGL gene and the FOXA2, PPP1R3B, NHLRC1 and GCK genes, which are related to metabolic processes. Conclusion: an initial clinical suspicion, through a good clinical history and the relevance of directed biochemical-metabolic-genomic studies, allows us to provide a correct diagnosis, treatment, and follow-up, bringing us closer to precision medicine.