Last reviewed: March 2026
Contents
MDM Templates
Acute Metabolic Crisis
Neonate/infant presents acutely ill with poor feeding, lethargy, and respiratory distress. Labs reveal significant metabolic derangement with anion gap metabolic acidosis, hypoglycemia, and/or hyperammonemia. Clinical picture highly concerning for inborn error of metabolism.
Differential includes urea cycle defect, organic acidemia, fatty acid oxidation disorder, maple syrup urine disease, and mitochondrial disease. Sepsis must be treated in parallel as it can coexist with or trigger metabolic crisis. Not consistent with simple viral illness or feeding difficulty given degree of metabolic derangement.[1]
Plan: D10 at 1.5x maintenance rate (goal 8-10 mg/kg/min glucose delivery). D10 bolus 5 mL/kg for documented hypoglycemia. Protein held. Empiric antibiotics started pending cultures. Metabolic team at nearest children’s hospital contacted emergently. Ammonia rechecked in 1-2 hours — if >300 μmol/L, arrange emergent dialysis. Admit to PICU, transfer to tertiary center with metabolic expertise.
Suspected IEM — Stable Presentation
Child presents with constellation of findings raising concern for underlying metabolic disorder — recurrent episodes of illness with fasting, developmental delay, failure to thrive, or unexplained mild metabolic derangements. Currently well appearing and hemodynamically stable.
Although stable now, IEM can decompensate rapidly with physiologic stress (infection, prolonged fasting). Metabolic workup obtained. Not consistent with isolated viral illness given the pattern of recurrent episodes and metabolic abnormalities.[2]
Plan: Metabolic labs sent (glucose, BMP, ammonia on ice, lactate, LFTs, urine organic acids, plasma amino acids, acylcarnitine profile). Metabolic team consulted to guide further evaluation. Family counseled on avoidance of prolonged fasting and red flags requiring immediate return (lethargy, persistent vomiting, rapid breathing, unusual urine odor). PCP notified of metabolic concern.
Clinical Education
When to Suspect IEM
Unexplained anion gap acidosis in a neonate is IEM until proven otherwise. Also suspect IEM with: refractory hypoglycemia, hyperammonemia at any level in a neonate, ketones in newborn urine (neonates do not normally produce ketones), and “sepsis” that is culture-negative and unresponsive to antibiotics.[1]
Timing patterns: Many IEMs present in the first days to weeks of life as the infant transitions from placental metabolism to independent feeding. Some (urea cycle defects, fatty acid oxidation disorders) present later during metabolic stress from illness or fasting. A normal newborn screen does NOT exclude all IEM.
Peculiar odors are diagnostic clues: maple syrup (MSUD), sweaty feet/old cheese (isovaleric acidemia), musty/mousy (PKU). Ask caregivers about unusual smells in urine or sweat.
The Metabolic Emergency Workup
Send everything at once — do not wait for results to start treatment.[2]
| Test | Key Points |
| Glucose | POC then serum. Treat <40 mg/dL (neonate) or <50 (infant) immediately |
| VBG/ABG | pH, bicarb, lactate. AG acidosis with no clear cause = IEM |
| Ammonia | MUST transport on ice to lab immediately. >100 is concerning, >300 = emergent dialysis |
| BMP, LFTs | Electrolytes, renal function, hepatic involvement |
| Urine organic acids | Refrigerate specimen. Any ketones in neonatal urine is abnormal |
| Plasma amino acids / acylcarnitines | Diagnostic for specific IEMs. Results take hours-days |
Glucose Management
Glucose is the single most important emergency treatment in IEM. Providing substrate halts catabolism, suppresses fatty acid oxidation, and stops production of toxic metabolites. This is the metabolic equivalent of giving oxygen in respiratory distress.[2]
Bolus: D10 5 mL/kg IV (= 500 mg/kg dextrose) for documented hypoglycemia. Infusion: D10 at 1.5x maintenance (goal glucose delivery rate 8-10 mg/kg/min). Recheck glucose every 1-2 hours. If hypoglycemia persists despite high-rate dextrose, suspect severe fatty acid oxidation defect.
Avoid IV lipid emulsions (Intralipid) acutely — many IEMs involve fatty acid oxidation defects. Use dextrose-only fluids until diagnosis is established.
Hyperammonemia
Ammonia is directly neurotoxic and causes cerebral edema, seizures, and death within hours if untreated. Any elevation in a neonate is abnormal. Levels 100-200: concerning, start treatment. Levels >300: emergent dialysis. Levels >500: imminent irreversible brain damage.[1]
Treatment ladder: (1) High-rate dextrose to suppress amino acid catabolism. (2) Hold all protein. (3) Sodium benzoate/phenylacetate (Ammonul) IV to activate alternate excretion pathways. (4) Lactulose via NG to reduce gut ammonia production. (5) Emergent dialysis if >300 or rising despite treatment.
Recheck ammonia every 1-2 hours. Do not assume stability — levels can rise rapidly. Metabolic team consultation is mandatory.
Acidosis Management
Anion gap metabolic acidosis in IEM results from accumulation of organic acids, lactate, and ketones. The primary treatment is glucose (halts catabolism and acid production). IV bicarbonate (0.5-1 mEq/kg slow push) only for pH <7.15 with symptoms, in consultation with metabolic team. Goal is pH >7.15, not normalization.[2]
Avoid lactated Ringer’s — use normal saline or dextrose-based fluids. Lactate will worsen acidosis in mitochondrial disease and organic acidemias. Allow the child to hyperventilate (respiratory compensation is physiologic, do not suppress it).
Getting Help
Do not manage IEM alone — contact the nearest children’s hospital with metabolic expertise immediately. Be concise: age, presentation, key labs (ammonia, pH, lactate, glucose), and what you’ve already done. The metabolic team will guide management and arrange transfer.[1]
New England Consortium Acute Illness Protocols provide evidence-based step-by-step management algorithms for specific IEMs. Bookmark these — they are the best available quick-reference resource for acute IEM management in the ED.
Disposition
Admit to PICU / transfer to tertiary center: Any acute metabolic crisis. Hyperammonemia. Severe acidosis (pH <7.2). Refractory hypoglycemia. Altered mental status. Need for dialysis.
Admit to pediatrics: Stable child with confirmed or suspected IEM requiring monitored workup. Known IEM patient with intercurrent illness needing glucose supplementation and metabolic monitoring.
Discharge (rare from ED): Known IEM patient with mild illness, tolerating PO, glucose stable, metabolic team agrees with outpatient management. Strict return precautions for vomiting, lethargy, or inability to eat.
References
- Häberle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. J Inherit Metab Dis. 2012;35(6):959-979. PubMed
- Saudubray JM, Sedel F, Walter JH. Clinical approach to treatable inborn metabolic diseases: an introduction. J Inherit Metab Dis. 2006;29(2-3):261-274. PubMed
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