PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels

Summary Aberrations in the glycosylphosphatidylinositol ( GPI )–anchor biosynthesis pathway constitute a subclass of congenital disorders of glycosylation, and mutations in seven genes involved in this pathway have been identified. Among them, mutations in PIGV and PIGO , which are involved in the late stages of GPI ‐anchor synthesis, and PGAP 2 , which is involved in fatty‐acid GPI ‐anchor remodeling, are all causative for hyperphosphatasia with mental retardation syndrome ( HPMRS ). Using whole exome sequencing, we identified novel compound heterozygous PIGO mutations (c.389C>A [p.Thr130Asn] and c.1288C>T [p.Gln430*]) in two siblings, one of them having epileptic encephalopathy. GPI ‐anchored proteins ( CD 16 and CD 24) on blood granulocytes were slightly decreased compared with a control and his mother. Our patients lacked the characteristic features of HPMRS , such as facial dysmorphology (showing only a tented mouth) and hypoplasia of distal phalanges, and had only a mild elevation of serum alkaline phosphatase ( ALP ). Our findings therefore expand the clinical spectrum of GPI ‐anchor deficiencies involving PIGO mutations to include epileptic encephalopathy with mild elevation of ALP .