Novel SLC6A9 variants in an adult presenting with GlyT1 encephalopathy.

Abstract

Only 14 individuals have been thus far described with GlyT1 encephalopathy due to biallelic variants in the SLC6A9 gene and the phenotypic picture is incomplete. Early mortality has been high, with only two known to survive into infancy. We report a 27-year-old individual who, to our knowledge, is the eldest person described with this ultra-rare disorder and who brings new phenotypic insights alongside potential prognosis for younger individuals. He is compound heterozygous for two novel SLC6A9 variants. He shares many unifying clinical features, including neonatal hypotonia with later hypertonicity, respiratory failure, exaggerated startle and arthrogryposis. Clinical course stabilised after early childhood. Perampanel was of significant benefit for the exaggerated startle. Significant visual loss is unexplained. It may relate to the essential role of GlyT1 in retinal amacrine cells, although this mechanism remains speculative.