2001 Associates' Presentations
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Unusual Cause of Acidosis
K. Hussain, M.D.
Steven Yale, M.D.
Marshfield Clinic, Marshfield, Wisconsin
A 44-year-old female presented with a one-month history of back pain treated with acetaminophen-oxycodone, one to two tables every six hours. Physical examination revealed a lumbosacral strain and fruity smell to her breath. Laboratory data were remarkable for CO2 level of 15 mEq/L, anion gap of 25 mEq/L, b-hydroxybutyrate of 5.3 mEq/L, lactate level of 0.9 mEq/l, acetaminophen level of 15 mg/mL, and normal salicylate and alcohol levels. ABGs showed pH 7.35 pCO2 18 mmHg, and a PaO1 123 mmHg on room air. Acetaminophen-oxycodone therapy was discontinued. A urine sample was submitted for organic acid by gas chromatography mass spectrometry and showed a pyroglutamic acid level of 554 mmol/mol (controls <70). The patient had a complete clinical and biochemical recovery.
Pyroglutamic aciduria (5-oxoprolinuria) is a rare cause of anion gap acidosis due to a deficiency of glutathione synthetase. The g-glutarnyl cycle is important in the synthesis and metabolism of gluathione. Normally, glutathione controls its own rate of production through feedback inhibition. Patients who are heterozygote for glutathione synthetase have reduced activity of this enzyme, normal basal glutathione levels and no clinical abnormalities. Drugs such as acetaminophen, flucloxacillin or vigabatrin are known to deplete glutathione store during toxic exposures or in susceptible hosts. Glutathione deficiency leads to overproduction of g-glutamylcysteine which is subsequently converted to 5-oxoproline. 5-Oxoproline accumulates because its rate of production exceed the metabolic capacity of the 5-oxoprolinase enzyme.
We believe that our patient was heterozygous for glutathione synthetase deficiency. She lacked the typical features of congenital glutathione deficiency such as chronic metabolic acidosis, hemolytic anemia and progressive cerebral and cerebellar degeneration.
Both gluathione content and duration of exposure to acetaminophen are important in determining susceptibility to this condition. In patients with unexplained high anion gap acidosis, acetaminophen and other potential drugs should be withdrawn and 5-oxoproline measured in the urine.
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