Acute metabolic decompensation

A previously well child (most often a neonate) who deteriorates suddenly: encephalopathy, hypotonia, vomiting, poor feeding, seizures, tachypnea, coma. The trigger is typically a feed, an intercurrent illness, a fast, or a protein / fat load. The bedside task is the inverse of an outpatient work-up: diagnosis and resuscitation run in parallel, and the lab results that come back ten hours from now are not the ones that decide the next ten minutes.

This page is the framework for "metabolic crisis" call. The condition-specific differentials live on dedicated pages (hyperammonemia, hyperlactatemia, hypoglycemia, anion gap acidosis); this page tells you which of those branches you're on within the first hour.

Classify the patient by lab phenotype within the first hour into one of six buckets. The bucket dictates both the differential and the treatment.

1. Hyperammonemia WITHOUT acidosis (often respiratory alkalosis)

→ Urea cycle defect. OTC deficiency (X-linked) is the prototype; also NAGS, CPS1, citrullinemia (ASS1), ASL. Detailed work-up on the hyperammonemia page.

2. High anion-gap metabolic acidosis WITH ketosis

→ Organic acidemia. Propionic acidemia, methylmalonic acidemia, isovaleric acidemia, glutaric aciduria type 1. Often with secondary hyperammonemia (organic acids inhibit N-acetylglutamate synthase) and neutropenia + thrombocytopenia mimicking sepsis in neonates.

3. Hypoketotic hypoglycemia

→ Fatty acid oxidation defect. MCAD, VLCAD, LCHAD / TFP, CPT2, carnitine transporter defects (CUD). The defining feature is inappropriately low ketones for the degree of hypoglycemia: in fasting, you should make ketones from fat, and these children can't.

4. Lactic acidosis predominant (high anion gap, lactate-dominant)

→ Mitochondrial / Leigh / PDH deficiency / gluconeogenic defects (GSD I). L:P ratio splits respiratory chain (high) from pyruvate / gluconeogenic defects (normal). See hyperlactatemia.

5. Maple-syrup odor + branched-chain amino acid elevation

→ Maple syrup urine disease (MSUD). Encephalopathy + ketosis + characteristic odor in earwax / urine; leucine elevation drives the brain edema. Treatment: BCAA-free formula + dialysis if severe.

6. Sepsis-mimicking neonate (severe acidosis + neutropenia + thrombocytopenia + encephalopathy)

→ Organic acidemia, especially propionic and methylmalonic acidemia. The neonate cultured for sepsis whose ammonia is 800 is the textbook case. Always send ammonia and a critical sample in a "septic" neonate before assuming infection.

This is the single most important practical rule on the page: before you give dextrose, draw a "critical sample." Hypoglycemic and catabolic states have transient labs that disappear within minutes of glucose. If you treat first and draw later, you lose the diagnosis.

Critical sample (acute decompensation or acute hypoglycemia)

• Glucose (point-of-care + lab)
• Ammonia (free-flowing, on ice, STAT)
• Lactate + pyruvate (free-flowing, on ice, STAT; L:P ratio)
• Venous / arterial blood gas + electrolytes (anion gap)
• Beta-hydroxybutyrate (ketones) and free fatty acids (FFA:BOH ratio is the FAO splitter)
• Insulin, C-peptide, cortisol, growth hormone (hyperinsulinism vs counter-regulatory failure)
• Plasma amino acids (citrulline, BCAAs, alanine, arginine)
• Plasma acylcarnitine profile (C3 → PA/MMA, C5 → IVA, C5OH → 3-MCC, C8 → MCAD, C14:1 → VLCAD, C16-OH/C18:1-OH → LCHAD/TFP)
• Urine organic acids (don't delay; even a wet diaper helps)
• Urine ketones (in hypoketotic hypoglycemia, dipstick is informative within minutes)
• CBC, LFTs, coagulation, lipase if visceral involvement suspected

Aliquot extra serum, plasma, and urine and save frozen for later assays.

While the critical sample is in the lab, start empiric stabilization. The goal is to stop catabolism.

1. NPO: stop protein intake immediately. Stop enteral feeds.
2. IV D10 + electrolytes at 1.5× maintenance to provide glucose substrate and suppress endogenous catabolism. Increase to D12.5 / D15 via central line if hypoglycemic.
3. IV lipids (Intralipid) for additional non-protein calories unless fatty acid oxidation defect is the working diagnosis (then lipids worsen the picture for LCHAD / VLCAD; safe for MCAD, but withhold until acylcarnitines back).
4. Ammonia scavengers if hyperammonemic: IV sodium benzoate + sodium phenylacetate (Ammonul), IV L-arginine (substrate for most UCDs distal to CPS1), levocarnitine.
5. Hemodialysis for ammonia > 500, severe lactic acidosis, severe MSUD, or rising values despite scavengers. CRRT is acceptable when hemodialysis unavailable, but slower.
6. Cofactors empirically while panels are pending: hydroxocobalamin (B12-responsive MMA), biotin (biotinidase / holocarboxylase synthetase), thiamine (MSUD intermediate / thiamine-responsive PDH), carnitine.
7. Treat the trigger: antibiotics if sepsis cannot be excluded, but don't anchor on infection alone in a "sick neonate" without a critical sample.
8. Genetics, metabolism, and intensive care consults early. Many centers have a 24/7 metabolic on-call who can interpret in real time.

• Don't give dextrose before drawing the critical sample. Hypoketotic hypoglycemia disappears with glucose, and you lose the FAO diagnosis.
• Don't give protein boluses (amino acid IV formulas, TPN with amino acids) until UCD and organic acidemia are excluded.
• Don't withhold ammonia scavengers waiting for the gene. Sodium benzoate / phenylacetate / arginine treat empirically; the lab confirms later.
• Don't anchor on sepsis. A "septic" neonate with persistent acidosis or altered mentation out of proportion to vital signs deserves a metabolic critical sample before antibiotics narrow the working diagnosis.
• Don't use valproate for seizures in any undiagnosed encephalopathy without ruling out POLG-related disorders and UCDs (valproate precipitates hepatic failure in POLG and unmasks OTC carriers).
• Tourniquet ammonia and capillary lactate are unreliable. Repeat free-flowing on ice and process STAT before chasing the gene.

1. Critical sample as above before dextrose.
2. Lab phenotype → bucket → bucket-specific work-up.
3. Brain MRI once stable (Leigh pattern, ACoA in OTC deficiency, basal ganglia injury in GA1, BCAA edema in MSUD).
4. Newborn screening re-check (positive screens flagged → confirm; negative screens can be false-negative if blood drawn before 24 hours, on TPN, or in transfused infant).
5. Targeted gene confirmation once the biochemical phenotype is known; rapid exome / genome in the NICU is increasingly first-line for unexplained neonatal encephalopathy.