Signs of Inborn Errors of Metabolism in neonates and infants

Prof. Gizewska begins by introducing the concept of IEM, a term first coined by Sir Archibald Garrod. These are genetic disorders that disrupt metabolic pathways, often presenting with non-specific symptoms like vomiting, lethargy, hypotonia, and jaundice. While individually rare, they are collectively common and may appear in any clinical setting. She stresses the need to take detailed family histories, asking about consanguinity, ethnic background, unexplained sibling deaths, or maternal complications like acute fatty liver during pregnancy.

A core message is that IEM should always be considered in full-term neonates who develop sepsis-like symptoms without risk factors or infection evidence. Prof. Gizewska explains how neonatal metabolic crises can be mistaken for more common conditions like sepsis, respiratory distress, or birth trauma. Key red flags include sudden deterioration after a symptom-free period, abnormal laboratory findings (e.g. metabolic acidosis, hyperammonemia, or hypoglycemia), and peculiar signs such as strange odors, cataracts, or hepatomegaly.

She categorizes IEMs into groups, particularly highlighting those that cause metabolic intoxication—such as organic acidurias, urea cycle defects, and galactosemia. These can trigger acute symptoms soon after birth due to toxic metabolite accumulation once placental clearance ends. Neurological signs such as poor feeding, altered tone, seizures, and respiratory instability are common initial presentations.

Diagnostic strategies include expanded newborn screening using tandem mass spectrometry (MS/MS), which can detect over 20 IEMs in asymptomatic infants. Where this is unavailable or delayed, clinicians should rely on selective screening: blood gases, ammonia, lactate, glucose, liver enzymes, and urine organic acids. Storing blood, urine, and CSF samples early can support further testing if needed.

Prof. Gizewska emphasizes that early diagnosis not only saves lives but also supports informed reproductive decisions in affected families. She urges pediatricians to place IEM high on the differential diagnosis list for any sick neonate and to act rapidly when suspicion arises—because many IEMs are treatable if caught early.

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