Reference Interval of Cerebrospinal Fluid-Adenosine Deaminase Enzyme in Apparently Healthy Subjects- A Retrospective Study in India

Background and Aims: The aim of the present study was to re-evaluate the upper limit of normal range (ULN) for adenosine deaminase (ADA) level in cerebrospinal fluid (CSF) of healthy subjects in Indian population. Materials and Methods: Posteriori strategy was used for reference population selection. Individuals whose CSF samples had come to the laboratory of Bhatia Hospital, Mumbai (India) for ADA estimation during the period of January 2015-October 2016. After database search, 130 subjects were selected. Hexokinase method for CSF-glucose, turbidometric method for total protein and enzymatic method using the ADA assay kit BSBE for CSF-ADA was used. Non-parametric methodology recommended by IFCC/CLSI for reference intervals calculation was adopted. The 2.5 and 97.5 percentile formed the lower and upper limits of Reference Interval. Results: ULN range of CSF-ADA for the total study cohort was 10.7 U/L, which was quite higher compared to the ULN provided in the reagent kit insert (5.0 U/L). Upon gender wise comparison, female showed higher median CSF-ADA activity compared to male (Male-7.2; Female-8.2 p=0. 01), but upon application of robust methods, ULN of CSF-ADA did not show significant differences (ULN in Male-12.3 and in Female-12.5). Age wise analysis revealed that with increasing age; ULN of CSF-ADA showed increasing  till the age of 50 years and then showed decreasing trend with further increase in age. Conclusions: ADA level of 10.7 U/L in CSF should be adopted as the upper limit of normal range and gender based partitioning is not recommended. Age should be considered during the interpretation of CSF-ADA results for making this diagnostic test more clinically relevant.