• 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      

• 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