Pediatric emergency medicine trisk 605

Diseases involving the same metabolic pathways or organelles usually share similar
features. Thus, recognition and treatment does not require specific knowledge of IEMs, but
rather a general understanding of diagnostic categories and disease pathways.
Most IEMs with potential for acute decompensation present in neonates or infants but may
present in older children and adolescents.
Common clinical manifestations of acute decompensation include vomiting, lethargy,
seizures, rapid deep breathing, hypothermia, or brief resolved unexplained event (BRUE).
Metabolic acidosis, respiratory alkalosis, hypoglycemia, and/or hyperammonemia are
laboratory hallmarks of IEM. Pretreatment samples should be sent for testing when possible
as laboratory studies may become normal with treatment.
Prompt emergency treatment of physiologic decompensation, using PALS or APLS
guidelines, correction of metabolic derangements, as well of precipitant causes of
decompensation are critical for optimizing outcome.

Current Understanding
IEMs are usually caused by single gene defects that result in abnormalities in protein, carbohydrate, fat,
or complex molecule metabolism. Most are due to a defect in, or deficiency of, an enzyme, enzyme
cofactor, or transport protein that results in a block in a metabolic pathway. Clinical effects are the
consequence of toxic accumulations of substrates before the block or intermediates from alternative
metabolic pathways and/or defects in energy production and utilization due to deficiency of products
beyond the block. Common clinical presentations of IEMs are detailed in Table 95.1 .
In the ED, evaluation and management of patients with undiagnosed but suspected IEM is usually
guided by suspicion of metabolic disease but does not require a specific diagnosis. Categories of IEMs
and their clinical and laboratory findings are detailed in Table 95.2 . Patients with an organic acidemia,
urea cycle defect, disorder of carbohydrate utilization or production, fatty acid oxidation defect,
mitochondrial disorder, or peroxisomal disorder are at greatest risk of acute, life-threatening
decompensation. Patients with congenital adrenal hyperplasia, detailed in Chapter 89 Endocrine
Emergencies , may also present with acute critical decompensation.
Toxic accumulation of substances results from disorders of protein metabolism (i.e.,
aminoacidopathies, organic acidemias, urea cycle defects), carbohydrate intolerance, and lysosomal
storage disorders. Defects in energy production or utilization result from disorders of glycogenolysis and

gluconeogenesis, fatty acid oxidation defects, and mitochondrial disorders. Peroxisomal disorders are a
diverse group of IEMs caused by defects of single or multiple peroxisomal enzymes, or of peroxisomal
biogenesis that result in toxic accumulations, energy deficiency, and/or defects in biosynthesis of
complex molecules. Other categories include disorders of metal metabolism, purine, and pyrimidine
biosynthesis (e.g., Lesch–Nyhan syndrome); cholesterol biosynthesis, heme, bile acid, and bilirubin
metabolism, lipoprotein metabolism, and glycosylation.


TABLE 95.1
COMMON PRESENTATIONS OF INBORN ERRORS OF METABOLISM a


Acute neonatal catastrophe
Septic appearing
Temperature instability
Apnea, tachypnea, cyanosis, respiratory failure
Bradycardia, poor perfusion
Irritability, lethargy, coma
Seizures
Poor feeding, vomiting
Hypertonia, hypotonia
Sudden infant death
Neurologic disturbance
Developmental delay, usually progressive, with or without loss of milestones
Autism
Learning disabilities, behavioral and/or emotional disturbances
Hallucinations, delirium
Ataxia, dizziness, headache
Lethargy, coma
Encephalopathy

Seizures
Movement disorder, posturing
Peripheral neuropathy
Stroke, stroke-like episode
Vision, hearing, speech impairment
Dementia
Cardiac failure/myopathy
Failure with cardiomegaly ± skeletal muscle weakness
Cardiac arrhythmia, syncope, sudden death
Pericardial tamponade, effusion
Gastrointestinal/hepatic dysfunction, failure
Poor feeding, food intolerances/aversion, failure to thrive
Chronic intermittent vomiting, decompensation out of proportion to illness
Chronic diarrhea
Abdominal pain
Pseudoobstruction
Acute pancreatitis
Hepatomegaly
Liver failure/hepatocellular dysfunction—jaundice (direct and/or indirect), coagulopathy, elevated liver
function tests
Myopathy
Muscle weakness, pain, cramping
Exercise intolerance
Psychiatric disturbance
Anxiety


Psychosis
Personality changes
Behavioral disturbances

Depression
Obsessive compulsive disorder
Delirium, hallucinations, schizophrenia
Biochemical disturbance
Acidosis—chronic or acute recurrent
Hyperammonemia with or without alkalosis
Hypoglycemia with or without ketonuria, hypoketosis
a Findings

may be in isolation or combination and may be either intermittent or progressive over time.

Clinical Considerations
Triage
IEM should be considered in any neonate or infant who is critically ill without known etiology.
IEM can present at any age with recurrent syndromes (stupor, lethargy), failure to thrive, unusual
odors, or unexplained neurologic findings.
Assessment
History. Poor feeding, frequent vomiting, failure to thrive, lethargy in the morning before feeding or with
delayed feeding, intractable seizures, hypothermia, or acute life-threatening events are common
presentations of acute decompensation episodes. Unusual dietary preferences, particularly protein or
carbohydrate aversion, or the waxing/waning of episodic symptomatology may indicate possible IEM in
an otherwise healthy child. Physiologic stressors such as fasting, fever, illness, trauma, or surgery may
precipitate symptoms, especially if the stressor induces a catabolic state. Intercurrent infection may result
in decompensation out of proportion to the illness. A history of multiple hospitalizations for lethargy and
dehydration with improvement following intravenous (IV) fluids and glucose is common. Psychomotor
developmental delay, especially with loss of milestones, is also concerning for an IEM.
Certain findings suggest particular categories of IEMs. Vomiting occurs with many IEMs but is a
prominent feature of organic acidemias and urea cycle defects. Lethargy progressing to coma is common
with amino acid disorders, organic acidemias, urea cycle defects, fatty acid oxidation defects, and certain
disorders of carbohydrate intolerance. IEM should also be considered in any child with unexpected,

unexplained sudden death, even without other history suggestive of IEM. Cerebral edema is particularly
common in maple syrup urine disease and disorders with elevated ammonia or severe hypoglycemia.
Rapid deep breathing resulting in respiratory alkalosis is a hallmark of urea cycle disorders while
metabolic acidosis is more commonly seen in organic acidemias.