Sialic acid (SA), N-acetylated derivatives of neuraminic acid, play a centr
al role in the biomedical functioning of humans. The normal range of total
sialic acid (TSA) level in serum/plasma is 1.58-2.22 mmol L-1, the free for
m of SA only constituting 0.5-3 mu mol L-1 and the lipid-associated (LSA) f
orms 10-50 mu mol L-1. Notably, considerably higher amounts of free SA are
found in urine than in serum/plasma (approximately 50% of the total SA).
In inherited SA storage diseases such as Salla's disease, SA levels are ele
vated many times over, and their determination during clinical investigatio
n is well established. Furthermore, a number of reports describe elevated S
A levels in various other diseases, tentatively suggesting broader clinical
utility for SA markers. Increased SA concentrations have been reported dur
ing inflammatory processes, probably resulting from increased levels of ric
hly sialylated acute-phase glycoproteins. A connection between increased SA
levels and elevated stroke and cardiovascular mortality risk has also been
reported. In addition, SA levels are slightly increased in cancer, positiv
ely correlating with the degree of metastasis, as well as in alcohol abuse,
diabetes, chronic renal failure and chronic glomerulonephritis. Several di
fferent mechanisms are assumed to underlie the elevated SA concentrations i
n these disorders.
The apparent non-specificity of SA to a given disease limits the potential
clinical usefulness of SA determination. In addition, some non-pathological
factors, such as aging, pregnancy and smoking, may cause changes in SA con
centrations. The absolute increases in SA levels are also rather small (sav
e those in inherited SA storage disorders); this further limits the clinica
l potential of SA as a marker.
Tentatively, SA markers might serve as adjuncts, when combined with other m
arkers, in disease screening, disease progression follow-up, and in the mon
itoring of treatment response. To become clinically useful, however, the ex
isting SA determination assays need to be considerably refined to reduce in
terferences, to be specific for certain SA forms, and to be more easy to us
e.