Hypophosphatasia (HPP) is primarily thought of as a childhood disorder with soft bones caused by poor skeletal mineralization with a wide range of severity. Typically the earlier the onset, the more severe the disease. Childhood disease ranges in severity from perinatal, to infantile, to severe childhood, to mild childhood, to odontohypophosphatasia. The severity does not worsen during childhood. Signs and symptoms may improve during the late teens through early adulthood only to recur in the 4th and 5th decades of life. In adults, HPP is typically associated with low bone mass, fractures, and tooth loss throughout adulthood. Joint pain and dysfunction are common and calcium can accumulate in soft tissues, hardening the tendons and ligaments, interfering with movement. Fractures are typically seen with soft bones, often in the feet, from poor skeletal mineralization (osteomalacia). Sometimes bone density can be measured as normal even though bones are deficient in mineral because the bone density scanners (DXA) cannot distinguish between mineralized and non-mineralized bone.
Hypophosphatasia is caused by mutations in the ALPL gene, which encodes a protein, alkaline phosphatase, necessary for bone mineralization. The complete absence of alkaline phosphatase leads to the accumulation of a molecule that blocks bone mineralization and is typically lethal or severe early in life. Individuals who carry only one ALPL gene copy with a mutation (all of us have two copies of each gene, with few exceptions) can develop a normal skeleton or present with low bone mass in adult life. They can pass the mutation to their offspring.
HPP is first suspected based on the clinical features noted above with early tooth loss before age 5 years as the common hallmark. Laboratory tests aid in the diagnosis; alkaline phosphatase activity, which is measured in routine blood tests, is typically below normal or near the lower limit of normal. Abnormally increased levels of the active form of vitamin B6 are also found in HPP because the altered alkaline phosphatase cannot modify this vitamin as it usually does. Often X-rays of the hands, wrists, and knees can be helpful in determining the severity of the disease in childhood. Many patients never require medical therapy (odontohypophosphatasia).
A genetic test will ascertain the diagnosis when the clinical findings are inconclusive. Genetic tests are now widely available; they are accurate and are more affordable. Some drug companies sponsor genetic testing which is free to the patient. Knowing about the genetic causes also helps with family planning, and in some cases, helps physicians determine the best therapy.
A good intake of calcium and vitamin D is useful as in osteoporosis; however, high doses of vitamin D are not helpful and can even be harmful. A therapy that replaces the missing alkaline phosphatase, asfotase alfa (Strensiq®) is available for children with HPP. Although not FDA-approved for use in adults with HPP (in the USA), if there is evidence of the disease from childhood, asfotase alpha can be prescribed in adults to improve bone mineralization. Bone Health Program providers and staff will work with you to devise the most appropriate management
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