Thiamine transporter-2 deficiency: outcome and treatment monitoring

[Background] The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.

Bibliographic Details
Authors: Ortigoza-Escobar, Juan Darío, Serrano, Mercedes, Molero, Marta, Oyarzábal, Alfonso, Rebollo, Mónica, Muchart, J., Artuch, Rafael, Rodríguez-Pombo, Pilar, Pérez-Dueñas, Belén
Format: article
Status:Published version
Publication Date:2014
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/125836
Online Access:http://hdl.handle.net/10261/125836
Access Level:Open access
Keyword:Thiamine transporter 2 deficiency
Biotin responsive basal ganglia disease
SLC19A3
Leigh syndrome
Lactic acidosis
Thiamine
Biotin
Striatal necrosis
Dystonia
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spelling Thiamine transporter-2 deficiency: outcome and treatment monitoringOrtigoza-Escobar, Juan DaríoSerrano, MercedesMolero, MartaOyarzábal, AlfonsoRebollo, MónicaMuchart, J.Artuch, RafaelRodríguez-Pombo, PilarPérez-Dueñas, BelénThiamine transporter 2 deficiencyBiotin responsive basal ganglia diseaseSLC19A3Leigh syndromeLactic acidosisThiamineBiotinStriatal necrosisDystonia[Background] The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.[Methods] We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature.[Results] At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring.[Conclusions] ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.Supported by Fondo de Investigación Sanitaria Grant PI12/02010 and PI12/02078; Centre for Biomedical Research on Rare Diseases, an initiative of the Instituto de Salud Carlos III, Barcelona, Spain; Agència de Gestio’ d’Ajuts Universitaris i de Recerca-Agaur FI-DGR 2014 (JD Ortigoza-Escobar).BioMed CentralCentro de Investigación Biomédica en Red Enfermedades Raras (España)Generalitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2015201520142015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/125836reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1186/1750-1172-9-92Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1258362026-05-22T06:33:51Z
dc.title.none.fl_str_mv Thiamine transporter-2 deficiency: outcome and treatment monitoring
title Thiamine transporter-2 deficiency: outcome and treatment monitoring
spellingShingle Thiamine transporter-2 deficiency: outcome and treatment monitoring
Ortigoza-Escobar, Juan Darío
Thiamine transporter 2 deficiency
Biotin responsive basal ganglia disease
SLC19A3
Leigh syndrome
Lactic acidosis
Thiamine
Biotin
Striatal necrosis
Dystonia
title_short Thiamine transporter-2 deficiency: outcome and treatment monitoring
title_full Thiamine transporter-2 deficiency: outcome and treatment monitoring
title_fullStr Thiamine transporter-2 deficiency: outcome and treatment monitoring
title_full_unstemmed Thiamine transporter-2 deficiency: outcome and treatment monitoring
title_sort Thiamine transporter-2 deficiency: outcome and treatment monitoring
dc.creator.none.fl_str_mv Ortigoza-Escobar, Juan Darío
Serrano, Mercedes
Molero, Marta
Oyarzábal, Alfonso
Rebollo, Mónica
Muchart, J.
Artuch, Rafael
Rodríguez-Pombo, Pilar
Pérez-Dueñas, Belén
author Ortigoza-Escobar, Juan Darío
author_facet Ortigoza-Escobar, Juan Darío
Serrano, Mercedes
Molero, Marta
Oyarzábal, Alfonso
Rebollo, Mónica
Muchart, J.
Artuch, Rafael
Rodríguez-Pombo, Pilar
Pérez-Dueñas, Belén
author_role author
author2 Serrano, Mercedes
Molero, Marta
Oyarzábal, Alfonso
Rebollo, Mónica
Muchart, J.
Artuch, Rafael
Rodríguez-Pombo, Pilar
Pérez-Dueñas, Belén
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Investigación Biomédica en Red Enfermedades Raras (España)
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Thiamine transporter 2 deficiency
Biotin responsive basal ganglia disease
SLC19A3
Leigh syndrome
Lactic acidosis
Thiamine
Biotin
Striatal necrosis
Dystonia
topic Thiamine transporter 2 deficiency
Biotin responsive basal ganglia disease
SLC19A3
Leigh syndrome
Lactic acidosis
Thiamine
Biotin
Striatal necrosis
Dystonia
description [Background] The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/125836
url http://hdl.handle.net/10261/125836
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1186/1750-1172-9-92
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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