New variant in the ALG13 gene responsible for the congenital disorder of Is-type glycosylation in a male patient

Abstract

Congenital disorders of glycosylation (CDGs) are a group of inborn errors of glycan metabolism with multi-systemic manifestations. More than 100 different types of CDGs have been reported. The form involving the asparagine-linked glycosylation 13 (ALG13) gene is an uncommon X-linked form of these pathologies.

Objective: To describe the clinical features in one patient with ALG13-CDG and to compare them with previously reported cases.

Clinical Case: A 11-years-old boy, child of consanguineous parents, with hypotonia, severe developmental delay, intellectual disability, feeding difficulties, congenital heart disease (patent ductus arteriosus and mitral regurgitation), without epilepsy or coagulation disorders. The metabolic screening showed unclear results, including N-glycosylation studies in plasma that were normal. Therefore, whole-exome sequencing (WES) was performed which identified a previously unreported variant in the ALG13 gene: c.428C > T (p.P143L) in hemizygous state; confirmed by Sanger sequencing. His mother was a carrier of the same variant.

Conclusion: This is the first report of a Colombian patient with ALG13-CDG without epilepsy. The findings in this patient broaden the phenotypic spectrum of ALG13-CDG known to date and support that Nglycosylation disorders may be present in normal biochemical analysis. WES has become a costeffective technique that allows the identification of disease-causing mutations in diseases with a broad phenotypic and genotypic spectrum.