Challenges in the Management of Inborn Errors of Metabolism in Low- and Middle-Income Countries

Abstract

Inborn errors of metabolism (IEMs) are a diverse category of inherited genetic illnesses caused by abnormalities in enzymes, transport proteins, cofactors, or metabolic pathways that lead to disruption of normal biochemical processes. Individual illnesses are rare but collectively they constitute an important cause of newborn morbidity, childhood mortality, developmental delay, neurological impairment and lifelong disability. In high-income nations, early diagnosis by neonatal screening and rapid treatment initiation has drastically improved patient outcomes. But these advances remain out of reach for many low- and middle-income countries (LMICs), where health systems are hampered by poor laboratory infrastructure, limited access to advanced diagnostic technologies, a shortage of trained health professionals, low public awareness, and the high cost of specialised treatment. This results in many affected children being diagnosed late, suffering permanent organ damage, severe disability or untimely death. Recent advances in tandem mass spectrometry, next-generation sequencing and precision medicine have revolutionised the diagnosis and management of IEMs worldwide, however their uptake in LMICs is still low. This review focuses on the burden of IEMs, the key challenges influencing diagnosis and management of IEMs in resource-limited settings, and pragmatic approaches to improve patient care through healthcare policy, laboratory strengthening, workforce development, expanded newborn screening, and international collaboration.