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Diseases

Genetic and Rare Diseases Information Center (GARD)

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Hypophosphatasia


Other Names for this Disease
  • Hypophosphatasia mild
  • Phosphoethanol-aminuria
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Cause


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What causes hypophosphatasia?

Mutations in the ALPL gene cause hypophosphatasia.[201]

The ALPL gene provides instructions for making an enzyme called alkaline phosphatase. This enzyme plays an essential role in mineralization of the skeleton and teeth. Mutations in the ALPL gene lead to the production of an abnormal version of alkaline phosphatase that cannot participate effectively in the mineralization process. A shortage of alkaline phosphatase allows several other substances (phosphoethanolamine, pyridoxal 5'-phosphate (a form of vitamin B6) and inorganic pyrophosphate), which are normally processed by the enzyme, to build up abnormally in the body. Researchers believe that a buildup of one of these compounds, inorganic pyrophosphate (PPi), underlies the defective mineralization of bones and teeth in people with hypophosphatasia.[191][201][200]

ALPL mutations that almost completely eliminate the activity of alkaline phosphatase usually result in the more severe forms of hypophosphatasia. Other mutations, which reduce but do not eliminate the activity of the enzyme, are often responsible for milder forms of the condition.[201]

The perinatal and infantile forms of hypophosphatasia are inherited as autosomal recessive conditions. In these cases, the patient receives one defective gene from each parent. Some more mild (childhood or adult) hypophosphatasia cases are also inherited this way. Other mild adult cases seem to be inherited in an autosomal dominant pattern (the patient gets just one defective gene, not two, transmitted from one of his/her parents). In this form, mild hypophosphatasia can occur from generation-to-generation.[191]

Individuals with hypophosphatasia and parents of children with hypophosphatasia are encouraged to meet with a genetic professional to learn more about the likelihood and severity of hypophosphatasia recurring in their families.

Last updated: 7/17/2013