title: Neurogenetic Aspects of Hyperphosphatasia in Mabry Syndrome.
abstract: An autosomal recessive syndrome of hyperphosphatasia (elevated circulating alkaline phosphatase (AP), seizures and neurologic deficits) was first described by Mabry and colleagues in 1970. Over the ensuing four decades, few cases were reported. In 2010, however, new families were identified and the syndromic nature of the disorder confirmed. Shortly thereafter, next generation sequencing was used to characterize causative defects in the glycosyl phosphatidylinositol (GPI) biosynthetic pathway, based partly on our understanding of how AP is anchored by GPI to the plasma membrane. Whether the seizures and cognitive defects seen in Mabry syndrome patients are attributable in part to the constant hyperphosphatasia is not known, as there are more than 250 other proteins dependent on GPI for their anchoring to the plasma membrane. However, Mabry syndrome may provide a new window on AP function in growth and development.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, davidec.cole@utoronto.ca.
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
authors.forename: Miles D
authors.initials: MD
authors.lastname: Thompson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000523:psychology*; D000469:Alkaline Phosphatase; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005190:Family; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000523:psychology*; D010760:Phosphorus Metabolism Disorders / Q000235:genetics* / Q000523:psychology*; D012640:Seizures / Q000235:genetics / Q000523:psychology; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D017261:Glycosylphosphatidylinositols; C548267:ALPL protein, human; D000469:Alkaline Phosphatase