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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. METHODS: We report the clinical follow-up after thiamine and biotin supplementation in four child...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099387/ https://www.ncbi.nlm.nih.gov/pubmed/24957181 http://dx.doi.org/10.1186/1750-1172-9-92 |
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author | Ortigoza-Escobar, Juan Darío Serrano, Mercedes Molero, Marta Oyarzabal, Alfonso Rebollo, Mónica Muchart, Jordi Artuch, Rafael Rodríguez-Pombo, Pilar Pérez-Dueñas, Belén |
author_facet | Ortigoza-Escobar, Juan Darío Serrano, Mercedes Molero, Marta Oyarzabal, Alfonso Rebollo, Mónica Muchart, Jordi Artuch, Rafael Rodríguez-Pombo, Pilar Pérez-Dueñas, Belén |
author_sort | Ortigoza-Escobar, Juan Darío |
collection | PubMed |
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. 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. |
format | Online Article Text |
id | pubmed-4099387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40993872014-07-17 Thiamine transporter-2 deficiency: outcome and treatment monitoring Ortigoza-Escobar, Juan Darío Serrano, Mercedes Molero, Marta Oyarzabal, Alfonso Rebollo, Mónica Muchart, Jordi Artuch, Rafael Rodríguez-Pombo, Pilar Pérez-Dueñas, Belén Orphanet J Rare Dis Research 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. BioMed Central 2014-06-23 /pmc/articles/PMC4099387/ /pubmed/24957181 http://dx.doi.org/10.1186/1750-1172-9-92 Text en Copyright © 2014 Ortigoza-Escobar et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ortigoza-Escobar, Juan Darío Serrano, Mercedes Molero, Marta Oyarzabal, Alfonso Rebollo, Mónica Muchart, Jordi Artuch, Rafael Rodríguez-Pombo, Pilar Pérez-Dueñas, Belén Thiamine transporter-2 deficiency: outcome and treatment monitoring |
title | 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_short | Thiamine transporter-2 deficiency: outcome and treatment monitoring |
title_sort | thiamine transporter-2 deficiency: outcome and treatment monitoring |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099387/ https://www.ncbi.nlm.nih.gov/pubmed/24957181 http://dx.doi.org/10.1186/1750-1172-9-92 |
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