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discarded pretreatment samples are likely to be more informative than those collected after therapy.
Collection of samples during acute illness is usually preferred to provocative testing by metabolic
challenge performed when the child is otherwise well because this method may not yield diagnostic
specimens and may be dangerous.
The confirmatory specific diagnosis of most IEMs requires additional specialized testing for abnormal
metabolites, perturbed enzymatic function, or molecular testing.
When a child dies in the ED and an IEM is suspected, it is extremely important to attempt to diagnose
that disease because of the possibility that asymptomatic family members are affected or future children
are at risk. Routine autopsy does not usually provide a definitive diagnosis of IEM but may rule out other
causes of death and offer clues. IEMs can be diagnosed in the child who has just died by collecting the
appropriate specimens ( Table 95.6 ). In some situations, exome sequencing, genome sequencing, or
metabolomics may be used to evaluate for an underlying cause of decompensation. This evaluation is
usually guided by specialty consultation. Most IEMs can be categorized based on findings of initial
laboratory evaluations. Nearly all patients with IEMs that present as acute life-threatening disease will
have hypoglycemia, metabolic acidosis, and/or hyperammonemia. These initial findings will guide
immediate treatment and further evaluation. Important exceptions are nonketotic hyperglycinemia
(usually presents within 48 hours of birth with lethargy, coma, seizures, hypotonia, spasticity, hiccups,
and apnea) and pyridoxine deficiency and folinic acid–responsive disorders (which present with
intractable seizures with or without encephalopathy as neonate).