Inborn errors of metabolism

Background

• Suspect in any sick neonate
• Newborn screening varies by state
• May present as late as early adulthood
• Clinical manifestations are due to accumulation of toxic metabolites
• Must rule-out sepsis (more common in these patients)

Clinical Features

Exam and history:

• Lethargy (secondary to hyperammonemic encephalopathy)
• Nausea/vomiting
• Difficulty feeding
• Seizure
• Unusual odors
• Hypotonia
• Encephalopathy
• Hypoglycemia
• Hepatic dysfunction

Differential Diagnosis

Sick Neonate

THE MISFITS

• Trauma
• Heart
  • Congenital heart disease
  • Hypovolemia
• Endocrine
  • hypoglycemia
  • Hypothyroidism
  • Congenital adrenal hyperplasia
• Metabolic
  • Sodium
  • Calcium
  • Glucose
• Inborn errors of metabolism
• Seizure
• Formula / feeding problems
  • Hyponatremia
  • Hypocalcemia
  • FPIES / Food protein-induced enterocolitis syndrome
• Intestinal Disasters
  • Duodenal atresia
  • Midgut volvulus
  • Necrotizing enterocolitis
  • Intussusception
• Toxin
• Sepsis

Evaluation

• Physical Exam:
  • Organomegaly
  • Neuro exam - tone, reflexes
  • Skin rashes
  • Eye exam
• Labs:
  • Glucose level
  • Ammonia
    • Should be <100 in normal neonate
  • Lactate and pyruvate (drawn at same time)
  • Chemistry, hepatic panel
    • Anion gap (if >20, suggests an organic acidemia)
    • May see hypoglycemia, metabolic acidosis
  • Urinalysis (for ketones) or beta hydroxybutyrate in serum (very helpful to obtain prior to giving dextrose in hypoglycemic patients, if possible)
  • CBC
    • multiple organic acidemias can cause cytopenias
  • VBG
  • CPK in older kids and adolescents
• Additional studies:
  • Consider head CT

Management

Must stop catabolism and acculmulation of toxins/ammonia

1. Keep NPO
   • Removes potential inciting metabolic substrates
2. IVF
   • Normal saline 20 mL/kg boluses
   • Once rehydrated, switch to IVF with dextrose (D10) at 1-2x maintenance
   • Increases renal excretion of toxic metabolites
3. Hyperammonemia
   • <500
     • sodium phenylacetate/sodium benzoate 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
   • >500
     • Dialysis
4. Sodium bicarbonate if acidotic

Cerebral edema

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

If seizing

• consider vitamin B6 (pyridoxine)

Subsequent Management

• Consider L-carnitine in conjunction with specialist, as some diseases may respond (but has side effects)

See Also

• Neonatal Resuscitation

References

Authors

Ross Donaldson