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- 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
1) BurtonBK: Inborn errors of metabolism in infancy: A guide to diagnosis. Pediatrics102:E69, 19982) Review of Neonatal Hemochromatosis by Dr. Yu Kawai |
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