Pontocerebellar hypoplasia represents a group of inherited progressive neurodegenerative disorders with prenatal onset, thus intersecting development with degeneration. All subtypes share common structural defects of the pons and cerebellum, evident upon brain imaging. Targeted therapy is non-existent, and most patients die during infancy (Namavar et al., 2011b). Mutations in any of three subunits of the TSEN complex, in the mitochondrial arginyl-tRNA synthetase gene, the RNA exosome component EXOSC3, and the vaccine related kinase are found in some cases (Budde et al., 2008; Edvardson et al., 2007; Renbaum et al., 2009; Wan et al., 2012). We recently implicated AMPD2 in PCH, causing a defect in protein translation due to guanosine triphosphate depletion (Akizu et al., 2013). The data implicate RNA maturation and protein synthesis defects in PCH, but also suggest further causes are yet to be identified.
