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
    
    



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

2) Review of Neonatal Hemochromatosis by Dr. Yu Kawai