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Inborn errors of metabolism are genetic diseases caused by mutations
in metabolic enzymes, nutrient transporters, and related genes.
Because metabolism is the foundation of basic processes such as
energy homeostasis, fuel storage, and growth, it is not surprising
that many inborn errors of metabolism present with severe, multisystem
failure culminating in shock, cardiorespiratory collapse, and coma.
Therefore, inborn error of metabolism is a crucial category of diseases
in pediatric emergency medicine and critical care. Their pathophysiology
involves a combination of disturbances emanating from the dysfunctional
metabolic pathway, including failure to produce energy and required
metabolites, accumulation of toxic intermediates, and complex effects
on global metabolism due to sequestration of cofactors.
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Inborn errors of metabolism are by definition chronic diseases,
which may present with acute, life-threatening metabolic dysfunction1 (Table 114-1). Many of these “decompensating” metabolic
conditions can be stabilized with rather straightforward interventions
if the clinician recognizes the presence of an inborn error of metabolism
and takes appropriate action. The difficulty and danger in decompensated
inborn errors of metabolism is that their relatively low incidence
and nonspecific symptoms at presentation may not trigger suspicion
of a metabolic disorder. However, a few simple analytical considerations
will prompt the astute clinician to recognize an inborn error of metabolism
in an acutely ill child. First, such children often have clues within
their clinical presentations that can be elicited by asking questions
like the ones in Table 114-2. If these questions
suggest the possibility of an inborn error of metabolism, the clinician
should ensure that several metabolic screening laboratory studies
(Table 114-3) are performed to add supporting
clinical information and to guide presumptive management and specialized
diagnostic testing.
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