Authors: Komal Uppal , Himani Kaushik , Namita Bhardwaj , Shivani Sharma , Sunil Kumar Polipalli , Somesh Kumar , Seema Kapoor

Abstract

Inborn errors of metabolism (IEMs) caused by a deficit of some specific metabolic pathways are phenotypically heterogeneous complex disorders. Although in recent years metabolomics has helped in understanding the pathophysiology of IEMs, its challenges and limitations such as false positives and negatives result in delayed diagnosis and postponed treatment. This leaves the physician with a large list of differential diagnosis among IEMs. Early and accurate diagnosis in case of suspicious IEMs can be lifesaving, especially for conditions those are treatable. Recently, next-generation sequencing (NGS)-based whole-exome sequencing proved to be an efficient technology in enhancing the accuracy of diagnosis of metabolic disorders, especially for complex disorders. It offers a broader range of disorders diagnosed at an affordable cost compared to metabolomics. The aim of this article is to provide insights into bridging metabolomics and NGS-based genomics to improve diagnostic yield in complex IEMs, while also emphasizing the role of genetic counselling in empowering families and improving patient quality life.

Keywords: Inborn errors of metabolism, Metabolomic, Genomics, Genetic counselling.