What are the key clinical features that may suggest an inborn error of metabolism in a paediatric patient?

Key clinical features suggesting an inborn error of metabolism (IEM) in a paediatric patient include:

• Acute or recurrent episodes of metabolic decompensation such as vomiting, lethargy, hypotonia, seizures, or coma, often triggered by fasting, illness, or stress.
• Developmental delay or regression where a child loses previously acquired skills or fails to meet milestones appropriately.
• Neurological symptoms including unexplained seizures, movement disorders, or abnormal muscle tone.
• Failure to thrive or poor growth without an obvious cause.
• Unusual odours in breath, urine, or sweat, which may be distinctive for certain metabolic disorders.
• Hepatomegaly or liver dysfunction presenting with jaundice or abnormal liver function tests.
• Multi-system involvement such as cardiomyopathy, renal tubular acidosis, or hematological abnormalities.
• Family history of consanguinity, unexplained infant deaths, or similar symptoms in siblings.

These features should prompt consideration of IEM and urgent metabolic investigations and specialist referral NICE CG89 Ibrahim et al. 2014Sharma & Prasad 2017. Early recognition is critical as some IEMs are treatable and early intervention can prevent irreversible damage.