Pediatric emergency medicine trisk 2449 2449
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300 mg/kg/day IV or PO), which enhances secretion of organic acids, should be considered for patients
with isovaleric acidemia. Patients with holocarboxylase synthetase, biotinidase deficiency, or propionic
acidemia may improve with biotin (10 to 40 mg/day given PO or NG), those with maple syrup urine
disease may benefit from thiamine, and those with methylmalonic academia may benefit from
hydroxocobalamin (vitamin B12 ; 1 mg IM). It is usually not imperative that these cofactor therapies be
administered in the ED. Antibiotics should be administered as clinically indicated for infection.
Administration of an oral, broad-spectrum antibiotic to reduce gut flora, a significant source of organic
acids, may be beneficial but usually is not initiated in the ED. Efficacy of emergent treatment is
monitored by ongoing assessment of mental status, fluid and cardiovascular status, signs of bleeding, and
measurement of electrolytes, glucose, ammonia, and blood gas levels every 4 to 6 hours until the patient
is stabilized. Resolution of metabolic crisis usually takes days to weeks. The New England Consortium of
Metabolic Programs details treatment for specific organic acidemias on their website
.
UREA CYCLE DEFECTS
Goals of Treatment
For urea cycle defects, the specific goals of acute treatment are to eliminate protein intake, avoid protein
catabolism, remove ammonia, and treat any precipitating illness.
Current Understanding
Disorders of the urea cycle result in toxic accumulation of ammonia generated by the catabolism of
protein. Urea cycle disorders include carbamoyl phosphate synthetase 1 deficiency, ornithine
transcarbamylase deficiency, citrullinemia, argininosuccinate lyase deficiency, and arginase deficiency.
Ammonia, in excess, is a neurotoxin that results in cerebral edema as well as brainstem dysfunction.
Clinical Considerations
Assessment
Patients with severe enzyme deficiency present within the first few days of life, following consumption
of protein in breast milk or formula. Those with partial deficiency usually present within the first few
months of life, but may present even as adults, after intake of a quantity of protein that exceeds their
metabolic capacity. The most severe forms include carbamoyl phosphate synthetase 1 deficiency and
ornithine transcarbamylase deficiency, which is the most common urea cycle defect and the only one with
X-linked inheritance. Female carriers for ornithine transcarbamylase deficiency may manifest clinical
disease due to skewed inactivation of their X chromosomes, but usually present later, including during
adolescence. The other urea cycle defects affect males and females similarly. Arginase deficiency
typically presents later in life, ranging from infancy to adulthood, as a neurologic syndrome with
developmental delay and progressive neurologic abnormalities and usually less severe hyperammonemia.
Presentation even later in life can be acute, severe, and even life threatening.
Acute manifestations are anorexia, irritability, lethargy, vomiting, ataxia, seizures, progressing to
coma, and death without appropriate emergent treatment. Duration of coma is a better predictor of
outcome than is serum ammonia concentration. With late-onset forms, symptoms, although similar, are
usually episodic and/or less severe and may include subtle findings such as failure to thrive in infants and
learning and attention deficits, personality and behavioral disturbances, and migraine-like headaches in
school-age children and adolescents. Level of alertness and cardiorespiratory status must be assessed.
Potential precipitating factors, such as infection, should be investigated. Hyperammonemia is a brainstem
respiratory stimulant that results in tachypnea. Respiratory alkalosis is common, sometimes with
secondary metabolic acidosis. Increased intracranial pressure due to hyperammonemia may produce
bradycardia and elevated blood pressure. Electrolytes, blood gas, glucose, AST, ALT, alkaline
