Inborn Errors of Metabolism Screening in Neonates: Current Perspective with Diagnosis and Therapy

Abstract

Inborn errors of metabolism (IEMs) are rare hereditary or acquired disorders resulting from an enzymatic deformity in biochemical and metabolic pathways influencing proteins, fats, carbohydrate metabolism, or hampered some organelle function. Even though individual IEMs are uncommon, together, they represent a diverse class of genetic diseases, with new issues and disease mechanisms being portrayed consistently. IEM includes the extraordinary multifaceted nature of the fundamental pathophysiology, biochemical diagnosis, molecular level investigation, and complex therapeutic choices. However, due to the molecular, biochemical, and clinical heterogeneity of IEM, screening alone will not detect and diagnose all illnesses included in newborn screening programs. Early diagnosis prevents the emergence of severe clinical symptoms in the majority of IEM cases, lowering morbidity and death. The appearance of IEM disease can vary from neonates to adult people, with the more serious conditions showing up in juvenile stages along with significant morbidity as well as mortality. Advances in understanding the physiological, biochemical, and molecular etiologies of numerous IEMs by means of modalities, for instance, the latest molecular-genetic technologies, genome engineering knowledge, entire exome sequencing, and metabolomics, have prompted remarkable advancement in detection and treatment in modern times. In this review, we analyze the biochemical basis of IEMs, clinical manifestations, the present status of screening, ongoing advances, and efficiency of diagnosis in treatment for IEMs, along with prospects for further exploration as well as innovation.

Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7‐year study in eastern coastal areas of China

“…The most common variants were c.1031A > G, c.1130C > T, and c.164C > T, consistent with Suzhou (Wang et al, 2019 ), Zhejiang (Huang et al, 2016 ), and Jining (Yang et al, 2020 ). Other FAMD, such as PCD, MCADD, GA‐II, and very long‐chain acyl CoA dehydrogenase deficiency (VLCADD), were relatively rare in this study, but they also lead to varying degrees of clinical severity, which cannot be ignored (Mukherjee & Ray, 2022 ).…”

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…An immunoassay for ceruloplasmin concentration on DBS for Wilson's disease was successfully modified and automated allowing for its inclusion on NBS panels [506] of births occur, it is becoming increasingly available in the private sector, including expanded testing. There continue to be data reviews and appeals for government recognition of NBS based on these data: an appeal based on positive experiences from regional (model) programs in Chandigarh, Goa, and Kerala [507]; an appeal for all hospitals in urban areas to initiate NBS for CH, CAH, and G6PD deficiency (the local common disorders) [508,509]; a call for the government to support expanded NBS due to increasing public awareness and large numbers of cases detected annually in regional programs [510]; a review of 1.5 decades of case detection data from three tertiary care centers in Bangalore supporting NBS [511]; a systematic review and metaanalysis of the prevalence, screen positivity rates, and etiology of NBS for CH [512]; an analysis of the biochemical basis, clinical manifestations, treatment advances, and present status of screening [513]; a study of the cost effectiveness and cumulative economic benefits of NBS for CH [514]; and a study to show general acceptance by the public, and the need for increased general awareness of NBS [515].…”