Inborn errors of metabolism

Background

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

Diagnosis

Exam and history:

• Lethargic (2/2 hyperammonia encephelopathy)
• Nausea/vomiting
• Difficulty feeding
• Seizure
• Unusual odors
• Hypotonia

Diagnosis

• Encephalopathy
• Hypoglycemia
• Hepatic dysfunction
• Nonspecific complaints: lethargy, irritability, N/V

Work-Up

• Ammonia
  • Elevated ammonia is common finding
• Chemistry
  • May see hypoglycemia, metabolic acidosis
• Lactate
• Ketones

Work-Up

• Glucose level
• UA (ketones)
• Chemistry
  • Anion gap a/w organic acidemias
• LFT
• Ammonia
  • Should be <200 in normal neonate (higher suggests urea cycle disorders)
• Lactate
• VBG

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

Treatment

• Must stop catabolism and acculmulation of toxins/ammonia
• IVF with Dextrose at 1-1.5x maintenace
• Stop feeding
• Dialysis (ammonia >500)
• NaBicarb if acidotic
• Consider L-carnitine in conjuction with specialist, as some diseases may respond (but has side effects)
• If seizing: consider Vit B6/pyroxidine

Treatment

• NS 20 mL/kg boluses
  • Increase renal excretion of toxic metabolites
• Keep NPO
  • Removes potential inciting metabolic substrates
  • Provide D10 at 2x usual maintenance rates
• Hyperammonemia
  • <500
    • (Na phenylacetate & Na benzoate) 250mg/kg in D10 over 90min; then 250 mg/kg/d infusion
    • Arginine 210mg/kg IV/IO in D10 over 90min; then 210 mg/kg/d infusion
  • >600
    • Dialysis
• Cerebral edema
  • Hyperammonemia is risk factor
    • Give mannitol 0.5gm/kg IV/IO
    • Do not give steroids (worsens hyperammonemia)

See Also

• Neonatal Resuscitation