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MG-142 Improved motor function with 5-hydroxytryptophan in a family with systemic serotonin deficiency, hemiplegic migraines and neurodegenerative course
  1. GA Horvath1,
  2. R Ye2,
  3. S Stockler-Ipsiroglu1,
  4. PJ Waters3,
  5. RD Blakely2,
  6. M Coulter-Mackie4
  1. 1Division of Biochemical Diseases, BC Children’s Hospital, Vancouver, BC, Canada
  2. 2Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
  3. 3Biochemical Genetics Laboratory, University of Sherbrooke, QC, Canada
  4. 4Department of Pediatrics, University of British Columbia, BC, Canada

Abstract

Background Serotonin’s role is multiple: controlling mood and sleep, modifying vascular resistance, modulating spinal segmental reflexes and nociception amongst others.

Case report We present a family with three affected siblings, presenting with hemiplegic migraines, spinal cord atrophy, progressive lower limb weakness and spasticity, who were found to have profoundly low CSF 5HIAA levels (25, 14, 18 nmol/L, ref 87–189) and low platelet serotonin levels. Their motor function and strength greatly improved with 5-hydroxytrypotphan (5HTP)/carbidopa treatment.

Platelet serotonin transporter function was diminished, and cytoskeletal aggregates were proven to keep membrane proteins in the non-soluble fractions. Whole exome sequencing revealed a novel variant in SRRM2 gene, supporting alternative splicing of many target genes. This protein is a component of the spliceosome and has multiple functions in the splicing process. It also plays an important role in pre-mRNA splicing and has a role in cell migration. Alternative splicing increases the complexity of mammalian transcriptomes since nearly all mammalian genes express multiple pre-mRNA isoforms. Full transcriptome analysis comparing RNA expression in two affected and one unaffected sibling revealed multiple differences in levels of RNA expression and splicing.

Conclusion Improvement of motor function with 5HTP/carbidopa proves yet another important role of serotonin as a signalling molecule probably through its action on G-protein coupled receptors.

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