What is hypophosphatasia? (Back to Top)

What are the symptoms of hypophosphatasia? (Back to Top)

The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities similar to another childhood bone disorder called rickets. Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Additional complications in infancy include poor feeding and a failure to gain weight, respiratory problems, and high levels of calcium in the blood (hypercalcemia), which can lead to recurrent vomiting and kidney problems. These complications are life-threatening in some cases.^[3]

The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Adult forms of hypophosphatasia are characterized by a softening of the bones known as osteomalacia. In adults, recurrent fractures in the foot and thigh bones can lead to chronic pain. Affected adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.^[3]

The mildest form of this condition, called odontohypophosphatasia, only affects the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss, but do not have the skeletal abnormalities seen in other forms of hypophosphatasia.^[3]

What causes hypophosphatasia? (Back to Top)

Mutations in the ALPL gene cause hypophosphatasia.^[3]

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.^[1][3][6]

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.^[3]

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.^[1]

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.

How is hypophosphatasia treated? (Back to Top)

In FY 2008, a research project listed in CRISP (Computer Retrieval of Information on Scientific Projects), a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other research institutions, looks at molecular mechanisms involved in hypophosphatasia. This project entitled, Molecular Pathogenesis and Treatment of Hypophosphatasia, is working to develop treatments for hypophosphatasia and other bone diseases. To read about this study, as well as others related to hypophosphatasia, click on the link below. In the "enter search terms" box, enter "hypophosphatasia". Then click "Submit Query."
http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen

Is hypophosphatasia treated differently if you have osteoporosis?  (Back to Top)

Having hypophosphatasia as a confirmed diagnosis may help patients avoid therapies for osteoporosis or osteomalacia that could be either ineffective or possibly harmful to them.^[8] To learn more about a potential treatment which has shown success for individuals with hypophosphatasia and reduced bone density, click here. 

How can I learn more about hypophosphatasia and/or osteoporosis? (Back to Top)