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An Integrated Workflow of Identification and Quantification on FDR Control-Based Untargeted Metabolome
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Targeted versus untargeted omics - the CAFSA story
Maria Del Mar Amador1, Benoit Colsch2, Foudil Lamari3,4
1Assistance Publique-Hôpitaux de Paris, Département de Neurologie, La Pitié-Salpêtrière University Hospital, Paris, France.
Journal of Inherited Metabolic Disease
|February 10, 2018
Summary
Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA) is a heterogeneous disorder. Genetic and metabolomics analyses link CAFSA to mitochondrial DNA alterations, including POLG mutations or Kearns-Sayre syndrome mechanisms.
Area of Science:
- Neuroscience
- Genetics
- Metabolomics
Background:
- Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA) was identified in 2009.
- This study aimed to further elucidate the underlying mechanisms of CAFSA.
Purpose of the Study:
- To investigate the genetic and metabolic basis of CAFSA.
- To identify potential biomarkers and pathogenic pathways associated with CAFSA.
Main Methods:
- Sequential application of untargeted and targeted omic approaches.
- Exome sequencing and mass spectrometry-based metabolomics on cerebrospinal fluid (CSF).
- Analysis of patient cohorts including CAFSA patients, unexplained encephalopathy, and controls.
Main Results:
- Identified decreased 5-methyltetrahydrofolate (5-MTHF) in some CAFSA patients.
- Discovered a common CSF metabotype in CAFSA patients, linked to mitochondrial energy homeostasis metabolites (acetyl-CoA and carnitine).
- Confirmed association with POLG mutations and a mechanism similar to Kearns-Sayre syndrome.
Conclusions:
- CAFSA is a heterogeneous clinical and biological entity.
- Mitochondrial DNA alterations are implicated in CAFSA pathogenesis.
- Metabolomics provides insights into CAFSA pathophysiology.
Keywords:
Cerebellar ataxiaExomeFolateMetabolomics. Cerebrospinal fluidMitochondrial diseaseSialic acidMore Related Videos
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