Here are seven cardinal clues to the presence of an inherited metabolic disease (“inborn error of metabolism”):
- Normal pregnancy and birth, but the infant begins to deteriorate after an asymptomatic interval (usually after the first 24 hours of life)
- Symptoms are precipitated or exacerbated by changes in metabolic state or dietary habits: feeding, starvation, dietary changes, or exertion.
- Progressively worsening dysmorphic features
- Unusual or suspicious family history: consanguinity or early death, particularly in infancy
- Peculiar odor
- Bizarre laboratory abnormalities (e.g., ammonia > 200 → urea cycle defects)
- Persistent or worsening symptoms despite a reasonable and standard initial workup and management (e.g., sepsis workup with empiric antibiotic treatment).