Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis
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 d...
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doaj-cc2f4123a8f24016a217b4503cb5b1a72020-11-24T20:48:21ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2017-09-011110.3389/fnins.2017.00534298813Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous MeningitisShayne Mason0Carolus J. Reinecke1Regan Solomons2Faculty of Natural Sciences, Centre for Human Metabolomics, North-West University, Potchefstroom, South AfricaFaculty of Natural Sciences, Centre for Human Metabolomics, North-West University, Potchefstroom, South AfricaDepartment of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South AfricaBackground: 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.http://journal.frontiersin.org/article/10.3389/fnins.2017.00534/fullgas chromatography-mass spectrometry (GC-MS)tuberculous meningitis (TBM)pediatriccerebrospinal fluid (CSF)amino acid profiling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shayne Mason Carolus J. Reinecke Regan Solomons |
spellingShingle |
Shayne Mason Carolus J. Reinecke Regan Solomons Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis Frontiers in Neuroscience gas chromatography-mass spectrometry (GC-MS) tuberculous meningitis (TBM) pediatric cerebrospinal fluid (CSF) amino acid profiling |
author_facet |
Shayne Mason Carolus J. Reinecke Regan Solomons |
author_sort |
Shayne Mason |
title |
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis |
title_short |
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis |
title_full |
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis |
title_fullStr |
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis |
title_full_unstemmed |
Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous Meningitis |
title_sort |
cerebrospinal fluid amino acid profiling of pediatric cases with tuberculous meningitis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2017-09-01 |
description |
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. |
topic |
gas chromatography-mass spectrometry (GC-MS) tuberculous meningitis (TBM) pediatric cerebrospinal fluid (CSF) amino acid profiling |
url |
http://journal.frontiersin.org/article/10.3389/fnins.2017.00534/full |
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