Treatment of genetic defects of thiamine transport and metabolism. (2nd July 2016)

• Record Type: Journal Article
• Authors: Ortigoza-Escobar, Juan Darío; Molero-Luis, Marta; Arias, Angela; Martí-Sánchez, Laura; Rodriguez-Pombo, Pilar; Artuch, Rafael; Pérez-Dueñas, Belén
• Is Part Of: Expert review of neurotherapeutics. Volume 16:Number 7(2016)
• Page Start: 755
• Page End: 763
• Publication Date: 2016-07-02
• Subjects: SLC19A3 -- SLC19A2 -- SCL25A19 -- TPK1 -- SLC35F3 -- SLC44A4 -- thiamine -- biotin -- Wernicke encephalopathy -- Leigh syndrome; Neuropharmacology -- Periodicals; 615.7805
• DOI: 10.1080/14737175.2016.1187562
• Languages: English
• ISSNs: 1473-7175

Abstract

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.