Related Experiment Video
Updated: Feb 21, 2026
Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis
Shayne Mason1, Carolus J Reinecke1, Regan Solomons2
1Faculty of Natural Sciences, Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa.
Insights
Tackling tuberculous meningitis (TBM) in children, this study identified five key amino acids in cerebrospinal fluid (CSF) using gas chromatography-mass spectrometry. These biomarkers show promise for earlier TBM diagnosis and treatment.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Tuberculosis remains a major global health threat, particularly in Africa.
- Pediatric tuberculous meningitis (TBM) is a severe neurological manifestation with high morbidity and mortality.
- Early diagnosis of TBM is challenging due to non-specific symptoms, leading to delayed treatment and poor outcomes.
Purpose of the Study:
- To investigate the biochemical profile of cerebrospinal fluid (CSF) in pediatric TBM cases.
- To identify potential biomarkers for improving early diagnosis of TBM.
- To elucidate the neuroinflammatory pathways involved in pediatric TBM.
Main Methods:
- Analysis of amino acid profiles in CSF from pediatric TBM patients and controls.
- Utilized gas chromatography-mass spectrometry (GC-MS) for sensitive and accurate analysis.
- Employed stringent quality assurance and statistical methods for biomarker identification.
Main Results:
- Five amino acids—alanine, asparagine, glycine, lysine, and proline—were significantly elevated in TBM cases.
- Elevated alanine linked to increased CSF lactate; lysine associated with lipid peroxidation.
- Other amino acids implicated in neurotransmission, glutamate-glutamine cycling, and ammonia metabolism.
Conclusions:
- CSF amino acid profiling via GC-MS offers a promising avenue for early TBM diagnosis.
- Identifying these biomarkers can facilitate timely treatment initiation.
- Further research into CSF biochemistry can improve management of pediatric TBM.
Abstract:
Background: In Africa, tuberculosis is generally regarded as persisting as one of the most devastating infectious diseases. The pediatric population is particularly vulnerable, with infection of the brain in the form of tuberculous meningitis (TBM) being the most severe manifestation. TBM is often difficult to diagnose in its early stages because of its non-specific clinical presentation. Of particular concern is that late diagnosis, and subsequent delayed treatment, leads to high risk of long-term neurological sequelae, and even death. Using advanced technology and scientific expertise, we are intent on further describing the biochemistry behind this devastating neuroinflammatory disease, with the goal of improving upon its early diagnosis. Method: We used the highly sensitive analytical platform of gas chromatography-mass spectrometry (GC-MS) to analyze amino acid profiles of cerebrospinal fluid (CSF) collected from a cohort of 33 South African pediatric TBM cases, compared to 34 controls. Results: Through the use of a stringent quality assurance procedure and various statistical techniques, we were able to confidently identify five amino acids as being significantly elevated in TBM cases, namely, alanine, asparagine, glycine, lysine, and proline. We found also in an earlier untargeted metabolomics investigation that alanine can be attributed to increased CSF lactate levels, and lysine as a marker of lipid peroxidation. Alanine, like glycine, is an inhibitory neurotransmitter in the brain. Asparagine, as with proline, is linked to the glutamate-glutamine cycle. Asparagine is associated with the removal of increased nitrites in the brain, whereas elevated proline coincides with the classic biochemical marker of increased CSF protein in TBM. All five discriminatory amino acids are linked to ammonia due to increased nitrites in TBM. Conclusion: A large amount of untapped biochemical information is present in CSF of TBM cases, of which amino acid profiling through GC-MS has potential in aiding in earlier diagnosis, and hence crucial earlier treatment.
