PGAP2 and Elevated circulating alkaline phosphatase concentration: Autosomal recessive mutations in PGAP2 cause Hyperphosphatasia with Mental Retardation 3 (HPMRS3 OMIM # 614207), an IGD that presents with variably penetrant hyperphosphatasia, developmental delay, seizures, microcephaly, heart defects, and a variety of neurocristopathies including Hirschsprung’s disease, cleft lip, cleft palate, and facial dysmorphia (Hansen et al., 2013; Jezela-Stanek et al., 2016; Krawitz et al., 2013; Naseer et al., 2016).