Here we report a novel mutation in PRPS1 leading to PRS-I deficiency in three-females from a family with a phenotype consisting of OA followed by RP in all cases, plus neurological features overlapping CMTX5 and Arts syndrome with variable presentation in the proband (IV:3) and her mother (III:2). The gene discussed is PRPS1; the disease is Lethal ataxia with deafness and optic atrophy.