Treatment of genetic defects of thiamine transport and metabolism

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Treatment of genetic defects of thiamine transport and metabolism

Publicated to:Expert Review of Neurotherapeutics. 16 (7): 755-763 - 2016-07-02 16(7), DOI: 10.1080/14737175.2016.1187562

Authors: Dario Ortigoza-Escobar, Juan; Molero-Luis, Marta; Arias, Angela; Marti-Sanchez, Laura; Rodriguez-Pombo, Pilar; Artuch, Rafael; Perez-Duenas, Belen

Affiliations

a Department of Child Neurology , Hospital Sant Joan de Deu, University of Barcelona , Barcelona , Spain - Author

a Department of Child Neurology, Hospital Sant Joan de Deu , University of Barcelona , Barcelona , Spain - Author

b Clinical Biochemistry, Hospital Sant Joan de Deu , University of Barcelona , Barcelona , Spain - Author

c Division of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics , Hospital Clinic , Barcelona , Spain - Author

d Departamento de Biologia Molecular , Centro de Diagnostico de Enfermedades Moleculares (CEDEM), Centro de Biologia Molecular Severo Ochoa CSIC-UAM, IDIPAZ, Universidad Autonoma de Madrid , Madrid , Spain - Author

e Centre for the Biomedical Research on Rare Diseases (CIBERER), ISCIII , Madrid , Spain - Author

e Centre for the Biomedical Research on Rare Diseases (CIBERER), ISCIII , Spain - Author

f Department of Child Neurology , Hospital General de Granollers , Barcelona , Spain - Author

a Department of Child Neurology , Hospital Sant Joan de Deu, University of Barcelona , Barcelona , Spain - Author

a Department of Child Neurology, Hospital Sant Joan de Deu , University of Barcelona , Barcelona , Spain - Author

Hosp Clin Barcelona, Dept Biochem & Mol Genet, Div Inborn Errors Metab IBC, Barcelona, Spain - Author

Hosp Gen Granollers, Dept Child Neurol, Barcelona, Spain - Author

ISCIII, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain - Author

Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa CSIC UAM, IDIPAZ, Ctr Diagnost Enfermedades Mol CEDEM,Dept Biol Mol, Madrid, Spain - Author

Univ Barcelona, Hosp St Joan de Deu, Clin Biochem, Barcelona, Spain - Author

Univ Barcelona, Hosp St Joan de Deu, Dept Child Neurol, Passeig St Joan de Deu 2, Barcelona 08950, Spain - Author

Abstract

Thiamine is a key cofactor for energy metabolism in brain tissue. There are four major genetic defects (SLC19A2, SLC19A3, SLC25A19 and TPK1) involved in the metabolism and transport of thiamine through cellular and mitochondrial membranes. Neurological involvement predominates in three of them (SLC19A3, SCL25A19 and TPK1), whereas patients with SLC19A2 mutations mainly present extra-neurological features (e.g. diabetes mellitus, megaloblastic anaemia and sensori-neural hearing loss). These genetic defects may be amenable to therapeutic intervention with vitamins supplementation and hence, constitutes a main area of research.We conducted a literature review of all reported cases with these genetic defects, and focused our paper on treatment efficacy and safety, adverse effects, dosing and treatment monitoring. Expert commentary: Doses of thiamine vary according to the genetic defect: for SLC19A2, the usual dose is 25-200 mg/day (1-4 mg/kg per day), for SLC19A3, 10-40 mg/kg per day, and for TPK1, 30 mg/kg per day. Thiamine supplementation in SLC19A3-mutated patients restores CSF and intracellular thiamine levels, resulting in successful clinical benefits. In conclusion, evidence collected so far suggests that the administration of thiamine improves outcome in SLC19A-2, SLC19A3- and TPK1-mutated patients, so most efforts should be aimed at early diagnosis of these disorders.

Keywords

biotinleigh syndromescl25a19slc19a2slc19a3slc35f3slc44a4tpk1wernicke encephalopathyAnemia, megaloblasticBiotinBrainHumansLeigh syndromeMembrane transport proteinsMutationScl25a19Slc19a2Slc19a3Slc35f3Slc44a4ThiamineTpk1Wernicke encephalopathy

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Expert Review of Neurotherapeutics due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology (Medical).

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.1. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Weighted Average of Normalized Impact by the Scopus agency: 4.88 (source consulted: FECYT Feb 2024)
Field Citation Ratio (FCR) from Dimensions: 5.95 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-14, the following number of citations:

WoS: 28
Scopus: 39
Europe PMC: 15
OpenCitations: 37

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