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A webinar with Prof. Maria Giżewska (metabolic paediatrician, Pomeranian Medical University, Szczecin, Poland) on spotting inborn errors of metabolism in neonates and infants — how to take the history, recognise the early signs, and avoid confusing metabolic disease with neonatal sepsis. For neonatologists, paediatricians and metabolic teams.
Inborn errors of metabolism are individually rare but collectively numerous, and about two-thirds present in the neonatal period. Their danger, Prof. Giżewska explains, is that a full-term newborn from an uneventful pregnancy can look and behave normally for hours, days or weeks and then deteriorate — because toxic metabolites, previously cleared across the placenta, take time to accumulate; the more toxic the compound (ammonia above all), the shorter the symptom-free interval. The clinical picture is non-specific and overlaps with sepsis, respiratory distress and birth trauma, so her central message is that sepsis in a full-term neonate with no risk factors should itself raise suspicion of a metabolic disease, and that inborn errors must not be placed at the end of the differential — waiting to exclude everything else can lose the patient. She walks through the history (young healthy parents, sporadic cases, consanguinity, ethnic background, and any unexplained infant deaths previously labelled sepsis or SIDS), the value of listening to the mother, and clues from the pregnancy such as HELLP syndrome or acute fatty liver, which can signal a fetus with a fatty-acid oxidation defect like LCHAD. The intoxication-type disorders — organic acidurias, urea cycle defects, and sugar intolerances such as galactosemia — present with neurological deterioration (poor feeding, vomiting, abnormal tone, involuntary boxing or pedalling movements), neurovegetative signs, or liver failure. Investigation begins with the septic screen plus simple, high-yield tests — blood gases, glucose, lactate and especially ammonia — and detailed urine examination, while blood, urine and CSF are stored for specialised analysis. Tandem mass spectrometry newborn screening detects many conditions but not all, and may need repeating if suspicion persists. She stresses that many of these disorders are treatable, that a diagnosis must be pursued even after death for the family's sake, and that the key is simply to remember these diseases.
After viewing this webinar, participants will be able to:
You often cannot on presentation alone, and the two can coexist — which is exactly the point. A full-term neonate with no infectious risk factors, negative bacteriology and negative inflammatory markers who was well and then suddenly deteriorated after a symptom-free interval should raise strong suspicion of a metabolic disease. Listen to the mother about the first symptoms and their timing. The safe approach is to think of both at once and not to place inborn errors at the end of the list, because waiting to exclude everything else can lose the patient.
Alongside the septic screen: blood cell count, pH and blood gases, electrolytes, glucose (looking for both hypo- and hyperglycaemia), simple liver function tests, lactate and — emphasised above all — ammonia. Ammonia is a potent neonatal brain toxin and should be measured in any newborn with severe sepsis or otherwise unexplained symptoms; note that haemolysis from difficult sampling can cause a falsely high result. Detailed urine examination (for example ketonuria with severe metabolic acidosis, suggesting organic aciduria) adds further clues.
Because in utero the placenta clears the toxic metabolites the baby cannot metabolise, and the mother processes them; after birth the baby must handle them alone, and they accumulate over time. Normal postnatal catabolism adds to this even without oral feeds. The interval before symptoms depends on how toxic the compound is — with ammonia in urea cycle disorders it can be just hours, whereas other disorders take days or weeks. The sudden, unexplained deterioration after an initial well period is the characteristic pattern.
Yes. Closing the case without a diagnosis is described as a mistake. The family has a right to know why their child died, and the answer directly affects their future family planning and reproductive risk — for example the at-least-25% recurrence risk in autosomal recessive conditions. A defined set of specimens (blood, urine, CSF and others) should be taken and stored at the time of death so that specialised metabolic investigation remains possible afterwards.