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ABSTRACT
Introduction: 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.
Areas covered: 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.
Declaration of interests
This research was supported by the Instituto de Salud Carlos III-FEDER (FIS PI12/02010, FIS PI15/00287); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), an initiative of the Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación, Spain); and Agència de Gestió d’Ajuts Universitaris i de Recerca-Agaur, (2014FI_B 01225) (JD Ortigoza-Escobar). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Supplementary material
Supplemental data for this article can be accessed here.