A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I

The thiamine transporter gene SLC19A2 was recently found to be mutated in t hiamine responsive megaloblastic anaemia with diabetes and deafness (TRMA, Rogers syndrome), an early onset autosomal recessive disorder. We now repor t a novel G1074A transition mutation in exon 4 of the SLC19A2 gene, predict ing a Trp358 to ter change, in a girl with consanguineous parents. In addit ion to the typical triad of Rogers syndrome, the girl presented with short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Both muscle and skin biopsies were obtained before high dose thiamine suppl ementation. While no mitochondrial abnormalities were seen on morphological examination of muscle, biochemical analysis showed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. In the patie nt's fibroblasts, the supplementation with high doses of thiamine resulted in restoration of complex I activity. In conclusion, we provide evidence th at thiamine deficiency affects complex I activity. The clinical features of TRMA, resembling in part those found in typical mitochondrial disorders wi th complex I deficiency, may be caused by a secondary defect in mitochondri al energy production.