Contents
Heterogeneous group of disorders that are inherited or occur as the result of spontaneous mutations and involve the failure of the metabolic pathways involved in either the break-down or storage of carbohydrates, fatty acids, and proteins.
Presentations
Common features:
Although all IEM presentations exist on a spectrum depending upon degree and type of enzyme involvement, inborn errors of metabolism have some common features.
- Neurologic abnormalities (80% cases): Developmental delay, loss of milestones, poor tone, poor suck, and seizures
- Gastrointestinal symptoms: Vomiting, hepatomegaly, food intolerance, diarrhea, food aversion, exercise intolerance, and dehydration.
- More than half of children have both neurologic and gastrointestinal abnormalities.
Unique presentations:
- Carbohydrate metabolism errors: Present early (typically in the neonatal period) and catastrophically. Clinically, they can be indistinguishable from septic neonates. These children cannot metabolize food to fuel, and the prognosis with severe early involvement is poor.
- Hypoglycemia
- Brady/and tachydysrhythmias
- Hypothermia or hyperpyrexia
- Seizures, and poor tone
- Excretion pathways defects: They often have elevations in ammonia and other metabolites.
- Intoxication, with lethargy
- Altered mental status, seizures, vomiting
- Vital sign abnormalities
- Stored energy metabolism errors: Children may appear well for prolonged periods of time and can be asymptomatic as long as they have an ongoing intake of carbohydrates. In the event of any gastrointestinal illness, a change in diet, or forgoing of night feeds, he or she will be unable to access stored energy adequately and will present with symptoms.
- Hypoglycemia or seizures.
Diagnosis
Inborn errors of metabolism should be considered in the differential of any child with neurologic and/or gastrointestinal findings. Inborn errors should also be considered in children with failure to thrive, recurrent feeding issues and formula changes, “reflux” or “gastroparesis,” autonomic instability, or behavioral or learning issues.
Diagnostic algorithm:
A battery of tests should be ordered when suspecting a metabolic condition including but not limited to – a blood gas, glucose, lactate, ammonia, LFTs, plasma amino acids, urine organic acids, plasma carnitine, plasma acylcarnitine, electrolytes, blood urea nitrogen, uric acid, complete blood count, and urine ketones (think rainbow tube set).
Management
Most patients who are ill with suspected inborn errors of metabolism require monitoring in an intensive care unit setting.
Immediate management:
- Aggressive resuscitation
- Nil per oral (NPO): Since the emergency provider cannot know which portion of the metabolic pathway is deranged, it is prudent to prevent the patient from utilizing his or her native pathways for carbohydrate metabolism, clearance of metabolites, or accessing of stored energy.
- Pure substrate (glucose) at a volume that obviates the need for the patient to break down glycogen or fatty acids. This should be accomplished with 10% dextrose solution at a one and a half maintenance rate
- Insulin (0.05 U/kg/hour to 0.2 U/kg/hour) to manage hyperglycemia
Hyperammonemia:
- Nitrogen scavengers (sodium benzoate or sodium phenylacetate)
- Dialysis (ammonia > 600μg/dl)