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Although many 'classic' causes of metabolic acidosis are known, including diabetic ketoacidosis, lactic acidosis and the ingestion of acid-generating poisons, the origin is often multifactorial and, indeed, often cannot be ascribed solely to such 'classic' causes or a single causative anion.
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The 'SIG' category does not in itself identify an individual causative anion (for example ketones), but rather recognizes the presence of unidentified anions.
Some causes may be obvious with a single contributing anion, such as a pure lactate acidosis, whereas other complex disorders may not have a single and identifiable, causative anion and only the strong ion gap (SIG) is elevated.
Despite this, a single causative gene is yet to be identified, largely due to substantial genetic heterogeneity.
Although the mutant and the mediator sequences differed in more than 28,000 nucleotide positions, our approach enabled pinpointing the single causative mutation.
However, our study provides a potential explanation for this finding by identifying the causative anion.
The first step in determining the likely etiology should be to determine the type of causative anion.
There is no single causative agent of bacterial vaginosis.
In a retrospective review of 851 ICU patients, we classified patients into categories representing the predominant causative anion associated with the metabolic acidosis [ 28].
Median severity of AGE cases with a NoV as single causative agent was 14, and with a RV as a single causative agent, median was 16.
Therefore the effect size of a single causative variant should be modest [ 22].
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