Thiamine transporter-2 deficiency: outcome and treatment monitoring

Orphanet Journal of Rare Diseases

Belén Pérez-Dueñas¹  Pilar Rodríguez-Pombo¹  Rafael Artuch¹  Jordi Muchart³  Mónica Rebollo³  Alfonso Oyarzabal¹  Marta Molero¹  Mercedes Serrano¹  Juan Darío Ortigoza-Escobar² 

[1] Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain;Department of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Passeig Sant Joan de Déu, 2, Esplugues, Barcelona 08950, Spain;Department of Neuroradiology, Sant Joan de Déu Hospital, University of Barcelona, Barcelona, Spain

关键词: Dystonia;    Striatal necrosis;    Biotin;    Thiamine;    Lactic acidosis;    Leigh syndrome;    SLC19A3;    Biotin responsive basal ganglia disease;    Thiamine transporter 2 deficiency;   

Others  :  861502
DOI  :  10.1186/1750-1172-9-92

 received in 2014-04-08, accepted in 2014-06-13,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Ortigoza-Escobar et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 6.

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