Background. The purpose of this review is to provide a differential di
agnosis for a low anion gap. Methods. We describe the anatomy of the a
nion gap, Also, we follow-up with a review of the English-language lit
erature describing the causes of a low anion gap. During the past 15 y
ears, the introduction and widespread clinical use of ion-selective el
ectrode methodology for measuring serum electrolyte values has caused
a major fall in the normal range of the anion gap from 12 mEq/L +/- 4
mEq/L to 6 mEq/L +/- 3 mEq/L; therefore, a new definition for a low an
ion gap is in order. Results, Based on current clinical data, an anion
gap value of < 3 mEq/L should be considered low A low anion gap is a
useful diagnostic tool, but its clinical significance is often unrecog
nized. Also, it may be a handy clinical clue for the diagnosis of life
-threatening intoxications or occult neoplasms, such as multiple myelo
ma. The baseline low anion gap may mask the identification of a high g
ap metabolic acidosis in certain patients. Conclusions. Interpretation
of a low anion gap can provide valuable clinical information.