Vianey Ordóñez-Labastida, Departmento de Genética, Instituto de Oftalmología Conde de Valenciana, Ciudad de México; Unidad de Diagnóstico de Enfermedades Raras, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México; Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México
Juan C. Zenteno, Departmento de Genética, Instituto de Oftalmología Conde de Valenciana, Ciudad de México; Unidad de Diagnóstico de Enfermedades Raras, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México: Facultad de Medicina, Departamento de Bioquímica, Universidad Nacional Autónoma de México, Ciudad de México. México
Inborn errors of metabolism (IEM) are inherited disorders resulting from genetic defects in proteins involved in breakdown or storage of fatty acids, carbohydrates and proteins. Collectively, IEM encompasses approximately 1000 different disorders and can affect up to 1 in 2000 births. While biochemical newborn screening programs have been successfully applied to early identify newborns with treatable IEM conditions and to reduce their associated morbidity and mortality, the great majority of known IEM are not recognizable through biochemical screening. In recent years, next generation DNA sequencing technologies (including sequencing of gene panels, exome sequencing, and genome sequencing) has revolutionized the genetic diagnosis of monogenic diseases, including IEM. Here, we present a narrative review with selected bibliography to show a general landscape about the status of NGS-based IEM diagnosis as well as its intrinsic limitations. NGS can detect newborns with metabolic diseases that may otherwise be clinically unrecognized until symptoms start. Importantly, a subgroup of these newborns will benefit from individualized medical management.
Keywords: Inborn errors of metabolism. Mutation. Exome sequencing. Massive DNA sequencing.