Author:

David H.Rubin

Signs and Symptoms

• Disorders may present with either a rapid decompensation or a chronic indolent course
• Neonates, initial presentation:
  • Asymptomatic
  • Hypothermia (mitochondrial defects)
  • Hypotonia/hypertonia (peroxisomal disorders)
  • Apnea (urea cycle defects, organic acidosis)
  • Seizures (peroxisomal disorders, glucose transporter defects)
  • Lethargy, coma (numerous)
  • Vomiting (numerous)
  • Poor feeding, growth (numerous)
  • Jaundice (galactosemia, Niemann-Pick C)
  • Hypoglycemia (galactosemia, maple syrup urine), hepatomegaly, liver failure
  • Dysmorphic features (lysosomal storage disorders, congenital adrenal hyperplasia, Smith-Lemli-Opitz)
• Older children, untreated:
  • Failure to thrive (urea cycle defects)
  • Dehydration (organic acidosis)
  • Vomiting (urea cycle defects and others)
  • Diarrhea (numerous)
  • Food intolerance (lipid defects, amino acid defects)
  • Lethargy (urea cycle defects)
  • Ataxia (urea cycle defects)
  • Seizures (numerous)
  • Mental retardation (phenylketonuria and others)

Essential Workup

Key is to consider in differential diagnosis:

• Deteriorating neurologic status
• Unexplained failure to thrive, with dehydration, persistent vomiting, or acidosis
• Shock unresponsive to conventional resuscitative measures

Diagnostic Tests & Interpretation

Differential Diagnosis

• Often misdiagnosed as sepsis, dehydration, failure to thrive, toxic ingestion, or nonaccidental trauma
• Infection:
  • Sepsis
  • Meningitis
  • Encephalitis
• Metabolic:
  • Reye syndrome
  • Hepatic encephalopathy
  • Hyperinsulinemia
  • Hormonal abnormality
• Renal:
  • Renal failure
  • Renal tubular acidosis
• Toxic ingestion
• CNS mass lesions
• Nonaccidental trauma

Prehospital

Initial Stabilization/Therapy

For altered mental status, administer Narcan, glucose (ideally after Accu-Chek and thiamine)

ED Treatment/Procedures

• Establish airway, breathing, and circulation
• Normal saline 10 mL/kg (neonates and patients with heart failure), 20 mL/kg (infants and children); avoid lactated Ringer and hypotonic fluid
• If hypoglycemic, give IV glucose bolus at 0.25-1.0 g/kg D10 for neonates and D10 or D25 if older; maintenance D10-D15 at rate of 8-12 mg/kg/min of glucose to maintain serum glucose level at 120-170 mg/dL
• After glucose bolus, start D10-D15 in ½ normal saline at 1-1.5 maintenance
  • If patient is severely hypoglycemic, give IV glucose bolus of D25
• Rehydrate if patient is hypoglycemic:
  • Restore normal acid-base balance
• Administer bicarbonate and /or potassium acetate slowly if pH is <7.0:
  • Initiate dialysis if severe acidosis does not improve quickly
• Increase urine output to help in removal of some toxins
• Initially, stop all oral intake; amino acid metabolites may be neurotoxic
• Treat severe hyperammonemia (≥300-600 mmol/L) with immediate dialysis or with ammonia-trapping drugs such as:
  • Arginine hydrochloride
  • Sodium benzoate
  • Sodium phenylacetate
  • Sodium phenylbutyrate
  • Doses vary with disease; consult metabolic physician before use
• Identify and treat intercurrent or precipitating infection/illness
• Consult metabolic physician when any child presents with suspected inherited metabolic disease

Medication

• Glucose 0.25-1.0 g/kg IV (neonates D10; others D25)
• For severe metabolic acidosis: Sodium bicarbonate: 0.25-0.50 meq/kg/hr up to 1-2 meq/kg/hr IV
• Other disease-specific drugs, including pyridoxine and levocarnitine as indicated

Disposition

Follow-up Recommendations

• Primary care physician
• Metabolic disease specialist

• Treat dehydration with normal saline fluid bolus:
  • Follow glucose level carefully; avoid hypoglycemia
  • Use bicarbonate cautiously and only consider if pH <7.0
  • Hemodialysis may be necessary for hyperammonemia

• AlfadhelM, Al-ThihliK, MoubayedH, et al. Drug treatment of inborn errors of metabolism: A systematic review . Arch Dis Child. 2013;98(6):454-461.
• El-HattabAW, SuttonVR. Approach to inborn errors of metabolism in pediatrics . Pediatr Clin North Am. 2018;65(2):19-20.
• El-HattabAW. Inborn errors of metabolism . Clin Perinatol. 2015;42(2):413-439.
• FernhoffPM. Newborn screening for genetic disorders . Pediatr Clin North Am. 2009;56(3):505-513.
• LeonardJV, MorrisAA. Inborn errors of metabolism around time of birth . Lancet. 2000;356(9229):583-587.
• LevyPA. Inborn errors of metabolism: Part 1: Overview . Pediatr Rev. 2009;30(4):131-137; quiz 137-138.
• LevyPA. Inborn errors of metabolism: Part 2: Specific disorders . Pediatr Rev. 2009;30(4):e22-e28.
• SaudubrayJM, Garcia-CazorlaA. Inborn errors of metabolism overview: Pathophysiology, manifestations, evaluation and management . Arch Argent Pediatr. 2018;65(2):179-208.
• WeinerDL. Metabolic emergencies. In: FleisherGR, LudwigS, HenretigFM, eds. Textbook of Pediatric Emergency Medicine. 6th ed.Philadelphia, PA: Lippincott; 2010.

ICD9

• 270.6 Disorders of urea cycle metabolism

• 270.9 Unspecified disorder of amino-acid metabolism

• 277.9 Unspecified disorder of metabolism

• 276.2 Acidosis

• 271.9 Unspecified disorder of carbohydrate transport and metabolism

• 277.5 Mucopolysaccharidosis

• 277.87 Disorders of mitochondrial metabolism

ICD10

• E72.9 Disorder of amino-acid metabolism, unspecified

• E72.20 Disorder of urea cycle metabolism, unspecified

• E88.9 Metabolic disorder, unspecified

• E87.2 Acidosis

• E74.9 Disorder of carbohydrate metabolism, unspecified

• E76.3 Mucopolysaccharidosis, unspecified

• E88.40 Mitochondrial metabolism disorder, unspecified

SNOMED

• 86095007 Inborn error of metabolism (disorder)

• 42930003 Inborn error of amino acid metabolism (disorder)

• 36444000 Disorder of the urea cycle metabolism (disorder)

• 70731005 Acidemia (disorder)

• 11380006 mucopolysaccharidosis (disorder)

• 20957000 Disorder of carbohydrate metabolism (disorder)

• 240096000 mitochondrial cytopathy (disorder)