Recognising Inborn Errors of Metabolism Beyond the Newborn Screening Net: A Practical Guide for the General Paediatrician and Neonatologist.

Abstract

Inborn errors of metabolism (IEMs) are individually rare but collectively significant contributors to neonatal and paediatric morbidity. While expanded newborn screening, urine metabolic screening and broad molecular testing have transformed diagnostic capability, a substantial proportion of IEMs remain outside the reach of these tools, and clinical suspicion at first contact, typically the general paediatrician or neonatologist, remains essential to timely diagnosis. This review offers a practical overview for the non-specialist clinician: the scope and limits of newborn and urine metabolic screening, clinical presentations that should prompt consideration of an IEM despite reassuring results, first-line biochemical investigations, the complementary role of molecular diagnosis, and current and emerging treatments. Family-centred communication and, where relevant, early palliative care integration are discussed alongside diagnosis and treatment. An illustrative case highlights the consequences of normal screening results in a child later diagnosed with a treatable metabolic condition. The review aimed to equip general paediatric and neonatal clinicians to maintain appropriate suspicion, initiate first-line investigations promptly and engage specialists in a timely manner, recognising that early diagnosis remains the single greatest determinant of outcome for children affected by IEMs.