Statement of the Problem: Inborn Errors of Metabolism (IEM) are a diverse group of monogenic enzymopathies disrupting vital biochemical pathways, leading to severe neurological, hepatic, and muscular sequelae. Despite major scientific advances, diagnostic inequity, lack of universal newborn screening, and limited access to advanced therapeutics—especially in low-resource settings,sustain preventable morbidity and mortality.

Methodology & Theoretical Orientation: A PRISMA-compliant systematic review of 21 key studies (2000–2024) across PubMed, Scopus, Embase, and Cochrane evaluated diagnostic and therapeutic modalities in the USA, UK, and India. Data synthesis combined random-effects modelling and narrative integration within a theoretical triad of clinical pathology, molecular genetics, and translational pharmacotherapy.

Findings: Tandem mass spectrometry achieved >98% diagnostic sensitivity, while next-generation sequencing reached up to 85% yield. ERT demonstrated 62.9% mean efficacy, with Gaucher and Pompe diseases showing 92% and 70% improvement, respectively. Gene therapy trials revealed 95% motor milestone attainment, though costs and access remain barriers. Mortality of untreated IEM exceeded 50% in developing regions.

Conclusion & Significance: Integrating biochemical and molecular diagnostics has revolutionized IEM management. However, equitable access through universal newborn screening, genomic databases, and affordable therapeutics remains essential for sustainable global health impact.

Birupaksha Biswas, MBBS, MD (Pathology), is a distinguished academician and diagnostician whose professional trajectory exemplifies intellectual rigor, integrative vision, and scholarly endurance. He is the author of The comic book of neuropathology, blood on the edge, pediatric hematopathology, pathology at the edge of certainty, integrative diagnostic pathology, The alchemy of lesions to name a few. His extensive corpus of over fifty-one publications in reputed national and international journals reflects sustained contributions to hematopathology, neuropathology, oncopathology, and translational diagnostics. Biswas’s scientific discourse harmonizes cytomorphology, molecular genetics, and clinical interpretation into a unified diagnostic framework. His academic philosophy is anchored not in self-proclamation but in precision, reproducibility, and the ethical pursuit of knowledge. Through the confluence of analytical depth and reflective inquiry, he transforms pathology into both a science of discernment and an enduring act of intellectual stewardship.