According to this review I found recently (H/T to Renal Fellow Network) the mechanism is an accumulation of 5-oxoproline (pyroglutamic acid) due to depletion of glutathione. It is believed to be rare although the true incidence is unknown and it may be under recognized. Malnourished individuals seem more susceptible.
The take-home message? Once in a while the search for the usual suspects in a case of wide gap acidosis (ketones, lactate, toxic alcohols, salicylates, etc) is unrevealing. Consider this entity in appropriate clinical circumstances. Stop the acetaminophen and the acidosis may resolve.
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