Acute neurological regression following fever as presenting sign of pontocerebellar hypoplasia type 2D ( mutation).

Pontocerebellar hypoplasia type 2D (PCH2D) is caused by mutations in the gene encoding O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (; chromosome 4p15.2). This is a key enzyme in the biosynthesis of selenoproteins, which act in maintaining antioxidant systems. To date, 26 patients with PCH2D have been reported, all with neurological involvement characterized by progressive pontocerebellar and cerebral atrophy. The present study reports on a patient with compound heterozygosity in the gene, including a novel missense variant, c.440G>A (p.Ser147Asn). The patient exhibited acute neurological regression following a vaccination-related fever, which is reminiscent of primary mitochondrial disease. In addition, the patient displayed severe spastic tetraparesis, convergent strabismus and postnatal onset of microcephaly, as well as recurrent blood lactate elevation. Brain MRI showed multiple alterations in the peri/supraventricular and subcortical white matter and progressive pontocerebellar and cerebral atrophy. A review of the clinical spectrum associated with mutations was conducted and the first report on a patient with mutations of acute neurological regression following a catabolic stressor at the onset of PCH2D was provided. This study broadens the genetic background of PCH2D and associated PCH2D phenotype, supporting the causal link between selenoprotein biosynthesis deficiency and mitochondrial disorders.