Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and sensorineural deafness

We report here a 6-year-old boy exhibiting severe dystonia, profound intellectual and developmental disability with liver disease, and sensorineural deafness. A deficient creatine peak in brain 1H-MR spectroscopy and high ratio of creatine/creatinine concentration in his urine lead us to suspect a creatine transporter (solute carrier family 6, member 8; SLC6A8) deficiency, which was confirmed by the inability to take up creatine into fibroblasts. We found a large ~ 19 kb deletion encompassing exons 5–13 of SLC6A8 and exons 5–8 of the B-cell receptor-associated protein (BAP31) gene. This case is the first report in which the SLC6A8 and BAP31 genes are both deleted. The phenotype of BAP31 mutations has been reported only as a part of Xq28 deletion syndrome or contiguous ATP-binding cassette, sub-family D, member 1 (ABCD1)/DXS1375E (BAP31) deletion syndrome [MIM ID #300475], where liver dysfunction and sensorineural deafness have been suggested to be attributed to the loss of function of BAP31. Our case supports the idea that the loss of BAP31 is related to liver dysfunction and hearing loss.

► We found a large ~ 19 kb deletion encompassing exons 5–13 of SLC6A8 and exons 5–8 of the BAP31 gene.
► This case is the first report in which the SLC6A8 and BAP31 genes are both deleted.
► Our case supports the idea that the loss of BAP31 is related to liver dysfunction and hearing loss.