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
- Lethargy, AMS, encephalopathy (often hyperammonemic)
- Seizure
- Hypotonia
- Nausea/vomiting, diarrhea
- Difficulty feeding
- Failure to thrive
- Unusual odors
- Hypoglycemia
- Organomegaly
- +/- Skin rashes
- +/- Eye findings
- Signs/symptoms of dehydration
- Infections
Differential Diagnosis
Sick Neonate
THE MISFITS [1]
- Trauma
- Heart
- Congenital heart disease
- Hypovolemia
- Endocrine
- Metabolic
- Sodium
- Calcium
- Glucose
- Inborn errors of metabolism
- Seizure
- Formula / feeding problems
- Intestinal Disasters
- Toxin
- Sepsis
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
- Anion gap (if >20, suggests an organic acidemia)
- May see hypoglycemia, metabolic acidosis
- 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
- Reassess after each bolus, as congenital heart disease may mimic symptoms of inborn errors
- 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
- Normal saline 10-20 mL/kg boluses
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