Document Detail


Cerebrospinal fluid alterations of the serotonin product, 5-hydroxyindolacetic acid, in neurological disorders.
MedLine Citation:
PMID:  20852934     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Although patients with low cerebrospinal fluid (CSF) serotonin metabolite levels have been reported, inborn errors of the rate-limiting enzyme of serotonin synthesis (tryptophan hydroxylase, TPH) have not been described so far. In this study we aimed to evaluate CSF alterations of the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) in patients with neurological disorders and to explore a possible TPH deficiency in some of them. A total of 606 patients (286 males, 320 females, mean age 4 years and 6 months, SD 5 years and 7 months) underwent CSF analysis of neurotransmitter metabolites by reverse phase high performance liquid chromatography. Results were compared with values established in a control population. Patients' medical records were reviewed to determine diagnosis and clinical features. A primary defect of biogenic amines was genetically investigated in indicated patients. Low 5-HIAA was seen in 19.3%. Of these, 22.2% showed inborn errors of metabolism (mitochondrial disorders being the most frequent at 10.2% of low 5-HIAA patients) and neurogenetic conditions. Other relatively frequent conditions were pontocerebellar hypoplasia (4.3%), Rett syndrome (4.3%), and among congenital nonetiologically determined conditions, epilepsy including epileptic encephalopathies (26.4%), leukodystrophies (6.8%), and neuropsychiatric disturbances (4.2%). Mutational analysis of the TPH2 gene, performed in five candidate patients, was negative. Although frequency of secondary alteration of 5-HIAA was relatively high in patients with neurological disorders, this finding was more frequently associated with some neurometabolic disorders, epileptic encephalopathies, and neuropsychiatric disturbances. No inborn errors of TPH were found. Due to serotonin's neurotrophic role and to ameliorate symptoms, a supplementary treatment with 5-hydroxytriptophan would seem advisable in these patients.
Authors:
Elisa De Grandis; Mercedes Serrano; Belén Pérez-Dueñas; Aida Ormazábal; Raquel Montero; Edvige Veneselli; Mercè Pineda; Verónica González; Francesc Sanmartí; Carmen Fons; Anna Sans; Bru Cormand; Luis Puelles; Antonia Alonso; Jaime Campistol; Rafael Artuch; Angels García-Cazorla
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-18
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  33     ISSN:  1573-2665     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  803-9     Citation Subset:  IM    
Affiliation:
Neurology Department, Hospital Sant Joan de Deu, Barcelona, Spain.
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