Examqo › Examqo library › Pediatrics › Neonatology · IMLE
Inborn errors of metabolism in the newborn
A newborn who was well for the first two days and then, after starting feeds, becomes lethargic, vomits, seizes or slips into coma — with negative cultures — suggests a metabolic disease; three tests orient you: a blood gas with anion gap, ammonia, and glucose with ketones.
Why it matters in the exam
The question presents "sepsis with negative cultures" and asks for the missing test — almost always ammonia. The laboratory pattern leads to the group: very high ammonia with respiratory alkalosis and no acidosis — a urea cycle disorder; metabolic acidosis with a high anion gap, ketosis and raised ammonia — an organic acidaemia; hypoglycaemia without ketones during fasting or illness — a defect of fatty-acid oxidation (e.g. MCAD deficiency).
Other clues: a maple syrup smell in the urine in MSUD, a "sweaty feet" smell in isovaleric acidaemia, jaundice with hepatomegaly, cataract and E. coli sepsis after milk feeds start in galactosaemia, and PKU, which causes no acute newborn illness but intellectual impairment and a "mousy" odour if missed. In OTC deficiency (X-linked) urinary orotic acid is high. In Israel newborn screening includes expanded metabolic screening.
Acute treatment follows the same spirit in all groups: stop protein or galactose, give glucose in large amounts (D10 at 8–10 mg/kg per minute) to stop catabolism, correct fluids and acidosis, and in hyperammonaemia give ammonia scavengers (sodium benzoate and sodium phenylacetate) and arginine. Ammonia above 500 µmol/L, or 250–500 that does not fall with treatment, is an indication for dialysis. The ammonia sample is taken free-flowing and sent on ice.
Key points
- Deterioration after feeds and negative cultures → metabolic disease.
- High ammonia without acidosis = urea cycle disorder.
- High anion gap acidosis with ketosis = organic acidaemia.
- Hypoglycaemia without ketones = fatty acid oxidation defect.
- Treatment: stop protein, high glucose, ammonia scavengers, dialysis for high ammonia.
Summary table
| Group | Typical laboratory | Clinical clue | Acute treatment |
|---|---|---|---|
| Urea cycle disorder (such as OTC) | Very high ammonia, respiratory alkalosis, no acidosis or ketosis | A boy in coma on day 2–5; high orotic acid in OTC | Stop protein, glucose, ammonia scavengers, arginine, dialysis |
| Organic acidaemias (MMA, propionic, isovaleric) | High anion gap acidosis, ketosis, raised ammonia, neutropenia | Sweaty feet smell in isovaleric | Stop protein, glucose, carnitine, dialysis if needed |
| MSUD | Ketosis, high leucine | Maple syrup smell, encephalopathy | Stop protein, glucose, dialysis for high leucine |
| Fatty acid oxidation defect (MCAD) | Hypoglycaemia without ketones | During fasting or illness; sudden death | IV glucose; avoid fasting |
| Galactosaemia | Urinary reducing substances, abnormal liver tests | Jaundice, hepatomegaly, cataract, E. coli sepsis | Stop breast milk and standard formula, switch to soy formula |
| PKU | High phenylalanine on screening | No acute illness; untreated — intellectual impairment | Low-phenylalanine diet from the first weeks |
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
The full version is open to subscribers of: Pediatrics, Medical licensing exam (IMLE).
Subscriber? Read the full topic Plans and prices 25 free questions
Sources
- Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision, 2019 — Acute hyperammonaemia management
- Nelson Textbook of Pediatrics, 22nd edition (2024) — An Approach to Inborn Errors of Metabolism
- Israeli Ministry of Health, national newborn screening programme (current) — Expanded metabolic screening by tandem mass spectrometry
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.