Extending the Concept of Advance Care Planning to the Perinatal Period.

Easier access to prenatal diagnostic procedures led to its widespread use as a screening measure. Hence, today it is more common for life-limiting illnesses to be diagnosed during fetal life. The concept of Advance Care Planning (ACP) provides a framework for caregivers, families and their multidisciplinary teams to anticipate and plan ahead for potential future medical decisions so that the affected children are reliably treated according to their parents' individual values and wishes. In the perinatal context, ACP also has the potential to tackle the needs of unborn or newborn children with life-limiting illnesses and their families better, avoid unnecessary and burdensome measures and focus upon goals that are valuable and meaningful to both child and family.

Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.