Variants in genes regulating thiamine metabolism in children in the Lao Thiamine study

The clinical symptoms of thiamine deficiency, or thiamine deficiency disorders (TDDs), present similarly in children with dietary thiamine deficiency and variants in genes of thiamine metabolism. In the rural north of Lao People's Democratic Republic there is a high incidence of TDDs, and the risk of TDDs differs with maternal ethnic group. While low dietary intake is a well-established risk factor for TDDs, the contribution of inborn errors of thiamine metabolism is unknown.

This study was an adjunct to the Lao Thiamine study, a prospective cohort study of children aged ≥ 21 days to <18 months with and without symptoms of TDDs. Buffy coat samples were selected from 17 hospitalised children with clinical signs/symptoms of TDDs and both echocardiogram and cranial ultrasound changes consistent with thiamine deficiency, and 14 frequency-matched healthy children in the community. Genomic DNA was isolated, and samples underwent next-generation sequencing of genes involved in thiamine metabolism. Ultimately, 22 of 31 selected residual samples provided adequate material to complete gene sequencing.

No pathogenic variants were identified in any of the 22 samples with completed gene sequencing. In a healthy infant, there was one variant of uncertain significance in LONP1, a gene implicated in an autosomal recessive disorder.

Variants in genes of thiamine metabolism are unlikely to be a common aetiology of TDDs in a region at high risk of dietary thiamine deficiency. Differences between ethnic groups in the incidence of TDDs are probably related to culture-specific dietary practices and socio-economic risk factors.