Metabolic Emergencies
Background
Overall incidence up to 1:1500
Not uncommonly seen in pediatric critical care
Generally autosomal recessive, some x-linked, some mitochondrial
Newborn screening required in all 50 states (21 diseases mandatory, some states with expanded screens to 30+ diseases)
Diagnosis
General Approach
Step 1: Clinical suspicion based on presentation
Infant with critical illness after period of normalcy
Nonspecific: poor feeding, lethargy, vomiting, failure to thrive, apnea, tachypnea
Can be indistinguishable from sepsis
Recurrent decompensation with fasting, jaundice, unexplained hemorrhage, developmental delay or regression, seizures, hypotonia
Family history of unexplained death or recurrent illness in siblings
Step 2: Appropriate diagnostic evaluation with the aid of genetics consultant
Figure 1: Laboratory Evaluations for Suspected IEM
Step 3: Appropriate stabilization and treatment while awaiting diagnostic results
Hyperammonemia
Vomiting, lethargy, encephalopathy
Urea cycle defects (respiratory alkalosis), some organic acidemias (metabolic acidosis), fatty acid oxidation defects
Eliminate protein intake
10% Arginine HCl 6 cc/kg
IV Ammonul
Dialysis (HD)
Metabolic Acidosis
Gap (>15) or no gap?
Organic acidemias
L-Lactic acidosis- evaluate Lactate: Pyruvate ratio (nl <25)
Normal or low pyruvate: High L:P: pyruvate carboxylase or respiratory chain defect
High pyruvate: Normal L:P: pyruvate dehydrogenase defect
Hypoglycemia
CH20 metabolism (ie GSD’s), hyperinsulinism, fatty acid oxidation defects
After prolonged fast, consider FAO defects: impaired ketogenesis (ie MCADD).
With jaundice, liver dysfxn, consider galactosemia
With hepatomegaly, consider glycogen storage deficiency
Courtesy of Richard Pierce, MD
Treatment
Clinical Pearls
Respiratory alkalosisàthink urea cycle defect, hyperammonemic encephalopathy
Galactosemia: E coli sepsis
Sweaty feet: isovaleric acidemia, glutaric acidemia
Hyperammonemia does not equal urea cycle defect
Summary
Maintain a high index of suspicion for IEM
Standard laboratory evaluation while critically ill is critical
Rational treatment including correcting abnormalities, providing calories/reducing catabolism, providing cofactors and/or scavenger
Don’t forget the basics (ie sepsis)
Multidisciplinary care
References
1) BurtonBK: Inborn errors of metabolism in infancy: A guide to diagnosis. Pediatrics102:E69, 1998