Thiamine transporter-2 deficiency: outcome and treatment monitoring

Abstract

BackgroundThe clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.MethodsWe 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.ResultsAt 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.ConclusionsThTR2 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.

Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone

“…Recently, Ortigoza-Escobar et al showed that treatment monitoring relied on whole blood thiamine diphosphate concentrations. 11 Overall, our findings would suggest that the combination of biotin plus thiamine is not superior to thiamine alone in the treatment of biotin-responsive basal ganglia disease. However, two limitations should be considered in the interpretations of our data: this study reports the short-term follow-up data of a single center open-label study; in our experience patients with BBGD may remain asymptomatic without treatment during several years, and second: the small number of patients included.…”

Leigh syndrome: One disorder, more than 75 monogenic causes

“…70 Unlike typical LS, patients with BTBGD can show significant clinical and neuroradiological improvement following administration of thiamine and high-dose biotin, particularly when commenced early in the disease course. 71 Patients with SLC19A3 mutations have been described as having "treatable" or "reversible" LS.…”

Thiamine Therapy for Dystonia Type 1

“…Genetic disorders of thiamine metabolism that lead to neurological diseases can be treated with highdose thiamine [11,12,13]. Recently, good results in sporadic degenerative diseases have been achieved with the same treatment [9].…”