Role of Molecular Genetics in the Diagnosis of Inborn Errors of Metabolism: A Review

inborn errors of metabolism (IEMs) are a heterogeneous category of inherited genetic illnesses caused by abnormalities in genes coding for enzymes, transporters or cofactors involved in metabolic pathways. These errors affect normal biochemical processes resulting in accumulation of hazardous metabolites, deficiency of necessary products and a wide spectrum of clinical symptoms, from moderate metabolic disturbances to life-threatening diseases. Early and precise diagnosis is important for prompt treatment intervention, prevention of irreversible organ damage and better results in patients. Conventional biochemical assays remain necessary in the first examination of suspected IEMs. However, breakthroughs in molecular genetics have revolutionised the diagnostic method, allowing for more precise and sensitive detection of disease-causing genetic variations. Molecular genetic techniques such as polymerase chain reaction (PCR), Sanger sequencing, next generation sequencing (NGS), whole exome sequencing (WES), whole genome sequencing (WGS) and multiplex ligation-dependent probe amplification (MLPA) have greatly improved the detection and characterisation of inherited metabolic disorders. These technologies enable early diagnosis, genotype–phenotype correlation, carrier discovery, prenatal diagnosis, newborn screening, genetic counselling and application of precision medicine. The present review is an attempt to provide an overview of the role of molecular genetics in diagnosis of inborn errors of metabolism. Molecular diagnostic techniques, clinical applications, advantages, limitations and emerging innovations are highlighted. Furthermore, the review addresses future approaches such as multiomics integration, artificial intelligence-guided variant interpretation and gene-based treatment methods, which are anticipated to revolutionise the diagnosis and management of hereditary metabolic illnesses. The continuing integration of molecular genetics into everyday clinical practice is expected to increase diagnosis accuracy, optimise patient care and play a major role in the development of personalised medicine.