STEPTRACKERBIOCHEMISTRY + PEDIATRICS | INBORN ERRORS | RAPID-FIRE REVIEW

Approach to the Sick Metabolic Infant

Four labs — glucose, ketones, ammonia, pH/lactate — sort almost every inborn error that presents with vomiting, lethargy or seizures.

FOCUS ON
Ask in order: Hypoglycemia? → ketones high (glycogen/gluconeogenesis defect, normal fasting) or low (fatty acid oxidation defect, hyperinsulinism). Hyperammonemia? → no acidosis (respiratory alkalosis) = urea cycle; with anion gap acidosis = organic acidemia. Lactic acidosis? → PDH, pyruvate carboxylase, mitochondrial, von Gierke. Then timing: first milk (galactose), weaning onto fruit (fructose), fasting/illness (MCAD).
LAB PATTERN
THINK
DISTINGUISHING CLUE
PAGE
Hypoglycemia + ↓ ketones
MCAD deficiency, carnitine deficiency, CPT defects
Fasting/illness trigger; abnormal acylcarnitine profile
10.01
Hypoglycemia + ↓ ketones + ↑ insulin
Congenital hyperinsulinism, infant of diabetic mother, insulinoma (older)
Low FFAs too (insulin blocks lipolysis)
Endocrine link
Hypoglycemia + ↑ lactate + hepatomegaly
Von Gierke (GSD I), fructose-1,6-bisphosphatase deficiency
Hours after a feed; ↑ TG, ↑ uric acid in von Gierke
8.07
Hypoglycemia + hepatomegaly, normal lactate
Cori (GSD III), Hers (GSD VI)
Milder; gluconeogenesis works
8.07
Hypoglycemia after starting fruit
Hereditary fructose intolerance
Vomiting, jaundice, liver failure after sucrose/fructose
8.06
Jaundice, cataracts, sepsis with first feeds
Classic galactosemia
Reducing substance in urine; E coli sepsis
8.06
↑ Ammonia, normal pH (resp. alkalosis)
Urea cycle defect
Orotic acid ↑ → OTC; normal → CPS I/NAGS
9.01
↑ Ammonia + anion gap acidosis + ketosis
Propionic or methylmalonic acidemia
Neutropenia, thrombocytopenia often; urine organic acids
9.04
Encephalopathy + sweet-smelling urine
MSUD
↑ Leucine on plasma amino acids
9.04
Lactic acidosis, normal glucose, neuro signs
PDH deficiency, mitochondrial disease
↑ Alanine (PDH); ragged red fibers, maternal pattern (mito)
8.02
Lactic acidosis + hypoglycemia, no hepatomegaly
Pyruvate carboxylase deficiency, biotinidase deficiency
Biotinidase: alopecia, rash, seizures (biotin-responsive)
8.04
Floppy infant + cardiomegaly, normal labs
Pompe
Macroglossia, ↑ CK
8.07
Floppy newborn + seizures + liver, ↑ VLCFA
Zellweger
Dysmorphic face, renal cysts
3.02
Normal newborn → regression by 6 months
Lysosomal storage disease (Tay-Sachs, Krabbe)
Cherry-red spot, startle, globoid cells
10.05

Mechanism — the four-lab sort

Glucose low?
→
Ketones lowFAO defect / hyperinsulinism
Ketones highGSD, gluconeogenesis, normal fasting
Ammonia high?
→
No acidosisUrea cycle
Anion gap acidosisOrganic acidemia
Lactate high?
→
PDH, PC, mitochondria, GSD I

Trigger timing

TRIGGER
THINK
REMOVE
First milk feeds
Galactosemia
Lactose/galactose
Weaning onto fruit/juice
Fructose intolerance
Fructose, sucrose, sorbitol
Fasting, viral illness
MCAD, GSD I
Avoid fasting
Protein load
Urea cycle, organic acidemia, MSUD
Protein (temporarily)

How it's tested

COMMON CONFUSIONUrea cycle defects cause respiratory alkalosis (ammonia stimulates breathing); organic acidemias cause metabolic acidosis with hyperammonemia.
THE TRAPLow ketones during hypoglycemia is abnormal — it means fat can't be burned (FAO defect) or insulin is suppressing lipolysis.
YOUR APPROACHRun the four labs in order, add timing and organ clues, then confirm with the specific test (acylcarnitines, urine organic acids, orotic acid, enzyme assay).

If you see… think…

Hypoketotic hypoglycemia after vomiting illness → MCAD
Hypoglycemia + lactic acidosis + big liver → von Gierke
Hyperammonemia + respiratory alkalosis → urea cycle defect
Hyperammonemia + anion gap acidosis → organic acidemia
Maple-syrup urine + encephalopathy → MSUD
Lactic acidosis + ↑ alanine, normal glucose → PDH deficiency
Jaundice + cataracts + E coli sepsis → galactosemia
Symptoms after starting fruit → hereditary fructose intolerance
Alopecia, rash, seizures, lactic acidosis → biotinidase deficiency
Floppy infant + huge heart → Pompe