ALPL

The ALPL gene provides instructions for making an enzyme called alkaline phosphatase. This enzyme plays an important role in the growth and development of bones and teeth. It is also active in many other tissues, particularly in the liver and kidneys. This enzyme acts as a phosphatase, which means that it removes clusters of oxygen and phosphorus atoms (phosphate groups) from other molecules.

Alkaline phosphatase is essential for the process of mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.

hypophosphatasia - caused by mutations in the ALPL gene

More than 190 mutations in the ALPL gene have been identified in people with hypophosphatasia. About 80 percent of these mutations change a single protein building block (amino acid) in the alkaline phosphatase enzyme. Other mutations insert or delete genetic material in the ALPL gene or change the way the gene's instructions are used to build the enzyme.

Mutations in the ALPL gene lead to the production of an abnormal version of alkaline phosphatase that cannot participate effectively in the mineralization of developing bones and teeth. A shortage of alkaline phosphatase allows substances that 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, underlies the defective mineralization of bones and teeth in people with hypophosphatasia.

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.