What is hypophosphatasia (HPP)?
Hypophosphatasia (HPP) is a rare genetic disorder characterized by the abnormal development of bones and teeth. These abnormalities occur due to defective mineralization, the process where bones and teeth take up minerals such as calcium and phosphorus. This deficient mineralization causes soft bones that are prone to fracturing and soft teeth that can lead to premature tooth loss.
Subtypes of HPP include:
- hypophosphatasia, adult
- hypophosphatasia, childhood
- hypophosphatasia, infantile
- hypophosphatasia, perinatal
- hypophosphatasia, prenatal benign
What are the symptoms of HPP?
The symptoms of HPP include the following:
- Metaphyses abnormality
- Ribs abnormality
- Teeth abnormality
- Bowing of the long bones
- Large fontanelles in infants
- Narrow chest
- Muscular hypotonia
- Recurrent fractures
What causes HPP?
HPP is caused by mutations in the ALPL gene, inherited in an autosomal recessive or autosomal dominant manner. The perinatal and infantile forms of HPP are inherited in an autosomal recessive manner. The childhood form can be either autosomal recessive or autosomal dominant. The adult form and odontohypophosphatasia typically are autosomal dominant disorders, but in rare cases can be inherited as an autosomal recessive trait.
How is HPP diagnosed?
HPP is often diagnosed after clinical evaluation, detailed patient history, and identification of characteristic symptoms. Testing for APL levels is key.
A diagnosis may be confirmed through:
- Blood test
- Imaging test
- Molecular genetic testing
What treatments are available for HPP?
The FDA approved Strensiq (asfotase alfa) as the first approved medical treatment for perinatal, infantile, and juvenile-onset HPP.
Other treatments include:
- Non-steroidal anti-inflammatory drugs (NSAIDs) to treat bone and joint pain.
- Vitamin B6 to help control specific seizures
- Orthopedic internal fixation