PGAP2 mutations and intellectual disability with elevated alkaline phosphatase

Red flags. Despite the availability of a large panel of metabolic and genetic tests as well as high-resolution neuroimaging, the cause of disease in the vast majority of patients remains unknown. This situation also applies for intellectual disability, where there is little to offer in terms of diagnostic procedures once patients are negative for array comparative genomic hybridization (array CGH). In clinical practice, we often hope that some minor clinical or biochemical features may lead us to the correct diagnosis, but in the majority of cases, these investigations lead nowhere. Now, in two back-to-back publications in the American Journal of Human Genetics, two papers describe PGAP2 mutations in patients with non-syndromal intellectual disability with elevated alkaline phosphatase.  Continue reading