X-linked pyruvate dehydrogenase complex deficiency due to a novel PDHA1 variant associated with structural brain abnormalities in a fetus

We report a case of pyruvate dehydrogenase E1 alpha subunit deficiency associated with a novel hemizygous PDHA1 variant presenting prenatally as multiple structural brain abnormalities in a male fetus. A healthy Finnish couple was initially referred to the Fetomaternal Medical Center because of suspected fetal choroid plexus cyst at 11 + 2 weeks of pregnancy. At 20 + 0 weeks, multiple abnormalities were observed with ultrasound including narrow thorax, slightly enlarged heart, hypoplastic cerebellum, absent cerebellar vermis and ventriculomegaly. Autopsy and genetic analyses were performed after the termination of pregnancy. The findings of macroscopic examination included cleft palate, abnormally overlapping position of fingers and toes and dysmorphic facial features. Neuropathological examination confirmed the absence of corpus callosum, cerebellar hypoplasia and ventriculomegaly. Nodular neuronal heterotopia was also observed. Trio exome sequencing revealed a novel hemizygous de novo variant c.1144C>T p.(Gln382*) in the PDHA1 gene, classified as likely pathogenic. We suggest that inherited metabolic disorders should be kept in mind as differential diagnoses in fetuses with structural brain abnormalities.     

Endemic hantavirus infection impairs the winter survival of its rodent host

The influence of pathogens on host fitness is one of the key questions in infection ecology. Hantaviruses have coevolved with their hosts and are generally thought to have little or no effect on host survival or reproduction. We examined the effect of Puumala virus (PUUV) infection on the winter survival of bank voles (Myodes glareolus), the host of this virus. The data were collected by monitoring 22 islands over three consecutive winters (a total of 55 island populations) in an endemic area of central Finland. We show that PUUV infected bank voles had a significantly lower overwinter survival probability than antibody negative bank voles. Antibody negative female bank voles from low-density populations living on large islands had the highest survival. The results were similar at the population level as the spring population size and density were negatively correlated with PUUV prevalence in the autumn. Our results provide the first evidence for a significant effect of PUUV on host survival suggesting that hantaviruses, and endemic pathogens in general, deserve even more attention in studies of host population dynamics.