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

• 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