Table 2

Biochemical tests for N2O-SACD

Test (approximate reference range)CommentApproximate sensitivity for N2O-SACD
Vitamin B12 (190–950 pg/mL)Serum vitamin B12 measurement is the standard first test. However, as N2O-SACD is a functional deficiency of B12, serum B12 concentrations are often within the reference range,13 16 19 27 as opposed to SACD due to pernicious anaemia or dietary deficiency where they are usually low.19 A lower B12 predisposes to N2O-SACD with smaller, shorter exposures to N2O.5 6 24 45 In our practice, serum B12 is normally in the lower third of the reference range or below; however, N2O-SACD can reportedly occur with high normal and even above normal B12 concentrations, including in patients who try to prevent N2O-SACD by taking oral or injectable B12 alongside recreational N2O.13 21 20–50%16 19 21 31
MMA (<0.28 µmol/L)MMA concentrations rise with falling concentrations of active B12 46; an MMA above 0.75 µmol/L is highly suggestive. Other causes of raised MMA include renal disease, hypovolaemia and small bowel overgrowth. Analysis of MMA is complex and so tends to be performed only in specialist laboratories. While all hospitals should have access to these services, the return of results may take several days.80–90%13 24 31
Homocysteine (<15 µmol/L)Elevated homocysteine concentrations can reflect B12 deficiency but may also occur in folate deficiency, renal failure and in patients with genetic polymorphisms.47 Hence, concurrent folate measurement is essential for interpretation of results. Samples for homocysteine measurement must be placed on ice after collection and transported to the laboratory promptly, which represents a significant barrier to its use.80–90%16 19 21 31
Holo-transcobalaminHolotranscobalamin is the ~25% of circulating B12 that binds to transcobalamin and is the form that can be transported into cells. Thus, holotranscobalamin is known as ‘active’ B12. Although there are no data on its use in N2O-SACD, its concentration is not changed by the presence of N2O,47 and it is likely to have similar sensitivity to standard B12 assays.Unknown
  • MMA, methylmalonic acid; N2O, nitrous oxide; N2O-SACD, nitrous oxide-induced subacute combined degeneration; SACD, subacute combined degeneration.