Historical Vignette: Hypophosphatasia: Molecular diagnosis of Rathbun's original case

Steven Mumm, Jonathan Jones, Patrick Finnegan, Michael P. Whyte

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27 Scopus citations

Abstract

In 1948, Dr. John Campbell Rathbun characterized the disorder "hypophosphatasia" when he reported paradoxically low levels of alkaline phosphatase (ALP) activity in blood and in several tissues from an infant who died with rickets and epilepsy, which seemed to reflect "a new developmental anomaly." Hypophosphatasia is now recognized to be an inborn error of metabolism featuring deficient activity of the tissue-nonspecific isoenzyme of ALP (TNSALP) caused by deactivating mutations in TNSALP. Here, we show, more than 50 years after Rathbun's case report, that analysis of the parental DNA indicates compound heterozygosity involving two missense mutations (G340A and A881C) in TNSALP caused the death of Rathbun's patient.

Original languageEnglish
Pages (from-to)1724-1727
Number of pages4
JournalJournal of Bone and Mineral Research
Volume16
Issue number9
DOIs
StatePublished - 2001

Keywords

  • Alkaline phosphatase
  • Inborn error of metabolism
  • Mutation
  • Osteoblast
  • Rickets

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