Hypophosphatasia (hypo-fahs-fuh-tay-shuh) or HPP is a metabolic bone condition that most often affects the development of bones and teeth. The signs and symptoms vary widely, with mild cases causing only dental abnormalities while the more severe types have life-threatening consequences. The hallmark of the disorder is bones that become soft or weakened, causing skeletal deformities, fractures, premature tooth loss and pain.
Typically, the earlier HPP symptoms become apparent, the more severe the condition. It is estimated that severe forms of HPP occur in approximately one of every 100,000 live births. While exact numbers are unknown, the more mild childhood and adult forms are probably more common and one out of every 200 Americans may be a carrier for HPP. Diagnosis is made through x-rays and blood testing and the disease is classified based on the age at which symptoms first appear.
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Perinatal HPP can be seen via fetal ultrasound before birth. Newborns with perinatal HPP often have short limbs, abnormal chest shape and soft skull bones. Perinatal is the most severe type of HPP and can involve life-threatening complications including pressure on the brain, seizures and respiratory complications such as difficulty breathing.
The most severely affected will fail to form a mineralized skeleton in the womb and are stillborn. Due to the severity of their condition, the life expectancy for those with perinatal HPP is measured only in days or weeks.
In the summer of 2015, the first-ever treatment for HPP was approved for use in Japan, Canada and the European Union (EU). Strensiq (asfotase alfa) is indicated for treatment of patients in Japan with HPP, as enzyme replacement therapy for patients with a confirmed diagnosis of pediatric-onset HPP in Canada and for long-term enzyme replacement therapy in patients with pediatric-onset hypophosphatasia HPP to treat the bone manifestations of the disease in the EU. The European approval applies to all 28 EU member states as well as Iceland, Norway, and Lichtenstein. The most common adverse reactions observed in clinical studies were injection site reactions and injection-associated adverse reactions. Most of these reactions were non-serious and mild to moderate in intensity. As always, patients should consult with their healthcare professionals about the treatment options that are right for them. Alexion, the makers of Strensiq, stated that the product will be available in Japan by late Q3 2015, in Germany in October and noted they are expecting regulatory decisions in the U.S. in the second half of 2015.
There continues to be research to learn more about HPP and to develop additional treatments for the disorder. Visit www.clinicaltrials.gov for more information and to learn about opportunities for HPP patients to participate in ongoing research.
Childhood HPP is less severe than the infantile form, but often causes delayed development notably with traditional milestones such as sitting, crawling or walking. Baby teeth fall out earlier than expected (before the age of five) and these children may have legs appear bowed and the skull and wrist or ankle joints may be misshapen.
Adult HPP is not typically diagnosed until middle age and can be confused with osteoporosis. As adult bones become soft, there is an increased risk of recurrent fractures, typically in the feet, and calcium deposits around the joints may cause pain and swelling. These adults may have had rickets as children or lost their baby teeth early and may be of short stature with bowed or deformed legs. Many adults diagnosed with HPP lead a very full life, and it is not considered a lethal form of the disease.
Odontohypophosphatasia is the most mild form of HPP and can affect both children and adults. While these patients do not exhibit skeletal abnormalities, they frequently have dental problems including decay and loss of teeth.
Pseudohypophosphatasia is a rare form of HPP where patients exhibit symptoms of the disorder but have normal blood levels of an enzyme (ALP) which is characteristically deficient in those with HPP. For more information on ALP, click here.
Benign Prenatal Hypophosphatasia
Another rare form of HPP, benign prenatal hypophosphatasia, can be identified while in utero via fetal ultrasound, but the skeletal deformities associated with the condition spontaneously improve during later stages of pregnancy or at birth.