Vitamin B6–responsive epilepsy due to inherited GPI deficiency

Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors many proteins to the cell surface. There are at least 26 genes involved in the biosynthesis of GPI-anchored proteins (GPI-APs).1 Recently, many inherited GPI deficiencies (IGDs) were found using whole-exome sequencing.2–4 The major symptoms of IGDs include mental retardation, epilepsy, coarse facial features, and multiple organ anomalies that vary in severity depending upon the degree of defect and/or position in the pathway of the affected gene. We clarified a mechanism of hyperphosphatasia, an elevated release of tissue-nonspecific alkaline phosphatase (TNAP, GPI-AP), seen in some of the patients with IGDs such as hyperphosphatasia mental retardation syndrome or Mabry syndrome caused by mutation in genes in the later stage of GPI biosynthesis.5