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Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease

Tobias B. Haack, Dirk Klee, Tim M. Strom, Ertan Mayatepek, Thomas Meitinger, Holger Prokisch, Felix Distelmaier
DOI: http://dx.doi.org/10.1093/brain/awu128 e295 First published online: 30 May 2014

Sir,

The research articles ‘Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy’ by Kevelam et al. (2013) and ‘Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome’ by Gerards et al. (2013) describe a novel disease entity of an infantile Leigh-like disorder caused by SLC19A3 mutations. In the study of Gerards et al. (2013) only two children out of 10 survived early childhood. These patients received different vitamins including thiamine and one child was treated with additional biotin during later clinical course. However, important information such as dosages and exact time point of the start of treatment has not been provided. Moreover, outcome in these patients was unfavourable. In the study of Kevelam et al. (2013) all patients died during the first years of life. No thiamine was given to these children.

SLC19A3 encodes a thiamine transporter (hTHTR2), which is essential for cerebral thiamine metabolism (Zeng et al., 2005). Impaired hTHTR2 activity due to SLC19A3 mutations is known to cause biotin-responsive basal ganglia disease (BBGD; OMIM 607483), which is a childhood-onset disorder characterized by episodes with encephalopathy and subsequent neurological deterioration (Zeng et al., 2005; Tabarki et al., 2013). Untreated, this disease may be fatal but supplementation of biotin and thiamine (both 10–15 mg/kg/day) is highly effective and prevents further disease progression (Distelmaier et al., 2013). Based on this knowledge, one might expect …

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