Hypophosphatasia

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

26 Scopus citations

Abstract

Hypophosphatasia is the rare, heritable form of rickets or osteomalacia that features low serum alkaline phosphatase (ALP) activity (hypophosphatasemia). Hypophosphatasemia in HPP is explained by a generalized reduction of activity of the "tissue-non-specific" isoenzyme of ALP (TNSALP) caused by loss-of-function mutation(s) within the TNSALP gene. The tissue-specific ALP isoenzyme genes are intact. In HPP, extracellular accumulation of the TNSALP substrate inorganic pyrophosphate (PPi), an inhibitor of mineralization, explains the skeletal disease. Characterization of this inborn error-of-metabolism verified a role for ALP in bone formation. The discoveries of elevated endogenous levels of three phospho compounds in HPP clarified the metabolic basis for this inborn-error-of-metabolism and the physiological role of TNSALP. HPP occurs worldwide. It is especially prevalent for inbred Mennonite families in Manitoba, Canada, where approximately 1 in 2500 newborns manifests severe disease, and approximately 1 in 25 individuals is a carrier. The prognosis for the various forms of HPP typically reflects the severity of the skeletal disease that corresponds with the age at presentation.

Original languageEnglish
Title of host publicationPediatric Bone
PublisherElsevier Inc.
Pages771-794
Number of pages24
ISBN (Print)9780123820402
DOIs
StatePublished - 2012

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