As I recently discovered, genetic counseling in a family with a child affected with D2 hydroxyglutaric (D2 HG) aciduria has become quite complicated. In addition to counseling on the possibility of the autosomal recessive form, caused by mutations in D2-HG dehydrogenase, now this counseling needs to include the possibility of dominant mutations (usually de novo, unless one parent is mosaic) in IDH2.
Clinical genetic testing for IDH2 is not widely available at this time, which further complicates the situation. Understanding the genetic cause of individuals with D2HG carries significant repurcussions on recurrence risk, and potentially treatment, and molecular diagnosis is imperative.
Hilary Vernon MD PhD