Inborn errors of metabolism

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Background

  • Clinical manifestations are due to accumulation of toxic metabolites
  • Suspect in any sick neonate
  • Newborn screening varies by state
  • May present as late as early adulthood
  • Must rule-out sepsis (more common in these patients due to organic acid-induced bone marrow suppression) and other physiologic stressors that might be precipitating decompensation

Clinical Features

Varies depending on disorder

Differential Diagnosis

Sick Neonate

THE MISFITS [1]

Evaluation

  • Evaluate for metabolic derangement +/- precipitant of decompensation
  • Labs:
    • Glucose level (most important/time sensitive!)
    • Ketones (urine or serum beta hydroxybutyrate)- helpful to obtain prior to giving dextrose in hypoglycemic patients, if possible
    • Ammonia
      • Should be <100 in normal neonate
    • BMP, LFTs
    • VBG
    • Lactate and pyruvate (drawn at same time)
    • CBC
    • Blood culture, urine culture, +/- CSF
    • Additional tests to aid in definitive diagnosis (consider setting aside blood sample on ice prior to dextrose admin)
      • Muscle function tests (e.g. CPK, LDH, myoglobin)
      • Serum/plasma pyruvate, amino acids, acylcarnitine profile
      • Urine organic acids, acylglycines, orotic acid
  • Consider head CT (evaluate for cerebral edema and alternate etiologies of symptoms)
  • Evaluate for alternate etiologies

Management

  • Patients with diagnosed inborn errors often have pre-established plans for "sick day" or emergency guidance
  • Early consultation with specialists

Resuscitate, stop catabolism/accumulation of toxins

  • Keep NPO
    • Removes potential inciting metabolic substrates
  • IVF
    • Normal saline 10-20 mL/kg boluses
    • IVF with dextrose (D10) and 0.45 or 0.9% NS at 1.5-2x maintenance
      • Aggressive hydration increases urinary excretion of toxic metabolites, dextrose provides metabolic substrate

Hyperammonemia

  • <500 micromoles/L
    • sodium phenylacetate/sodium benzoate (Ammonul) 250mg/kg in D10 over 90min; then 250mg/kg/d infusion
    • Arginine 210mg/kg IV/IO in D10 over 90min; then 210mg/kg/d infusion
    • +/- carnitine, 400 mg IV/IO in consultation w/specialist
    • May require dialysis if refractory/severe

Acidosis

  • Sodium bicarbonate 0.5 mEq/kg/h if pH <7.0 [2]
    • Reserve for severe and/or refractory acidosis due to potential side effects of sodium overload, cerebral edema, cardiac dysfunction
  • Caution intubating any child in metabolic crisis due to potential worsening of acidosis

Cerebral edema

  • Hyperammonemia is risk factor
    • Mannitol 0.5gm/kg IV/IO
    • Do not give steroids (worsens hyperammonemia)

Seizure

  • consider vitamin B6 (pyridoxine) in addition to usual care

Infection/Sepsis

  • Consider empiric antibiotics in all infants in metabolic crisis

Dispo

  • Admit or transfer to tertiary care children's hospital

See Also

References

  1. Brousseau T, Sharieff GQ. Newborn emergencies: the first 30 days of life. Pediatr Clin North Am. 2006 Feb;53(1):69-84, vi.
  2. Tintanelli's

Authors:

Ross Donaldson