Have questions? Visit https://www.reddit.com/r/SNPedia


From SNPedia

Hypophosphatasia is a rare, and sometimes fatal metabolic bone disease. Clinical symptoms are heterogeneous ranging from the rapidly fatal perinatal variant, with profound skeletal hypomineralization and respiratory compromise to a milder, progressive osteomalacia later in life.Wikipedia

The characteristic diagnostic finding is subnormal serum activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), which is caused by one of over 200 genetic mutations in the ALPL gene. Genetic inheritance is autosomal recessive for the perinatal and infantile forms but either autosomal recessive or autosomal dominant in milder forms. The prevalence of hypophosphatasia is not known. One study estimated the live birth incidence of severe forms to be 1:100,000.Wikipedia

Because severe hypophosphatasia arises from a very large spectrum of mutations (primarily in European populations) and there is no prevalent mutation, genetic diagnosis is best performed by extensive sequence analysis of the gene. Some mutations that may be somewhat more frequent, or are at least tested on common DTC microarray platforms include:

  • rs121918007, Glu174Lys or Glu191Lys; perhaps the most common mutation in Caucasians
  • rs387906525, 1559delT; perhaps the most common mutation in Japanese