2. The normal concentrations of ammonia and other nitrogenous compounds in blood and other body fluids - Concentration of glutamine

Next to ammonia, levels of glutamine are of greatest interest in patients with hyperammonaemia for reasons that we have already discussed.

Unfortunately, glutamine cannot be analysed in dried blood spots because it is too unstable. This is the reason why, currently, this parameter cannot be used for newborn screening.

Glutamine has to be measured in plasma (or in serum) where it is the most abundant amino acid with a range of concentration between 400 and 800 μmol/l (much depending on the lab which does the analysis). In patients with hyperammonaemia, levels can rapidly rise to millimolar concentrations.

Importantly, glutamine might be very rapidly converted to glutamate within the sample due to the function of the enzyme glutaminase. Thus, you should always consider the concentration of glutamate when you interpret the level of plasma glutamine.

It is clear that most often both ammonia and glutamine are elevated concomitantly. Whenever this is not the case, you need to think about an explanation. To some extent, glutamine concentrations might help to guide differential diagnosis. The following table lists the most important situations of hyperammonaemia with or without glutamine elevations.

Glutamine can also be assessed in CSF and this provides useful additional information. Often, concentrations in CSF are more elevated than in plasma and levels might rise to > 5000 μmol/l. Again, here you need to consider the level of CSF glutamate which usually is not detectable; if glutamate is present in CSF you should think of contamination of the CSF sample by blood.

Investigation of glutamine and other amino acids in urine is not helpful in hyperammonaemia because it reflects the tubular reabsorption rather than the situation in plasma. The only exception is inborn errors of metabolism that arise from defects of single tubular amino acid transporters, which is the case with lysinuric protein intolerance (defect in SCL7A7 gene leading to renal loss of dibasic amino acids arginine, lysine and ornithine and result in interruption of the urea cycle).

EXPERT ADVICE

The normal concentration of plasma glutamate is about 70-150 μmol/l (but this is different in every lab so check reference levels in your lab). Elevations of glutamate with concomitant decrease of glutamine concentrations are often due to pre-analytical problems (haemolysis, storage and long transport of the sample). Other important parameters to detect pre-analytical problems are the combination of aspartate and asparagine (aspartate is high and asparagine low in a badly kept sample because of an asparaginase action), the combination of ornithine and arginine (ornithine is high and arginine low in badly kept samples because of arginase action) and the free cystine levels (low in badly kept samples because cystine is bound to proteins).