Definition blood (a routine test) that is low in HPP. genetic counseling to explain the likelihood and However, it is important that the doctors use severity of HPP recurring in their families. (HPP) is an inherited appropriate age ranges for normal when metabolic (chemical) that results interpreting an ALP level. Prognosis from low levels of an enzyme called (ALP). Enzymes are proteins that Prevalence The outcome following a diagnosis of HPP is act in the body’s chemical reactions by breaking variable. In general, the earlier the diagnosis is down other chemicals. ALP is normally present It has been estimated that severe forms of HPP made the more severe the skeletal in large amounts in bone & in the liver. In HPP, occur in approximately one per 100,000 live manifestations. Cases detected in the womb or abnormalities in the gene that makes ALP lead to births. The more mild childhood and adult forms with severe deformity is made before six months production of inactive ALP. Subsequently, are probably somewhat more common. About of age, some infants have a downhill and fatal several chemical – including one out of every 200 individuals in the United course, others survive and may even do well. Phosphoethanolamine, phridoxal 5’-phosphate (a States may be a carrier for HPP. When diagnosed during childhood, there can be form of vitamin B6) and inorganic presence or absence of skeletal deformity from phrophosphate- accumulate in the body and are Depending on the severity of the skeletal underlying , but premature loss of teeth found in large amounts in the blood and urine. It disease, there may be deformity of the limbs and (less than 5 years of age) is the most common appears that the accumulation of inorganic chest. can result if chest distortion is manifestation. Adults may be troubled by pyrophosphate is the cause of the characteristic severe. Recurrent fractures can occur. Teeth recurrent fractures in their feet and painful, partial deficient calcification of bones in infants and may be lost prematurely, have wide pulp (inside) fractures in their thigh bones. children (rickets) and in adults (). chambers, and thereby be predisposed to Nevertheless, the severity of HPP is remarkably cavities. Treatment For Hypophosphatasia broad-ranging from patient-to-patient. Inheritance Factors For many years, treatment has been generally Symptoms & Diagnosis directed toward preventing or correcting the symptoms or complications. Procedures such as The severe perinatal and infantile forms of HPP rodding, especially in adults, can be helpful with The most severely affected, fail to for a skeleton are inherited as autosomal recessive conditions. painful partial fractures in their thigh bones. in the womb and are stillborn. The most mildly The patient receives one defective gene from Expert dental care and physical therapy are affected patients may show only low levels of each parent. Some more mild (childhood or recommended. Monitoring levels such as alkaline ALP in the blood, yet never suffer bony problems. adult) HPP cases are also inherited this way. phosphatase, B6, and calcium (which are/can be In general, patients are categorized as having Other mild adult and odontohypoposphatasia outside the limits of normal in hypophosphatasia) “perinatal”, “childhood”, or “adult” HPP depending cases seem to be inherited in an autosomal should be undertaken and are dependent upon on the severity of the disease which in turn is dominant pattern (the patient gets just one how the patient is being treated. reflected by the age at which bony manifestations defective gene, not two, transmitted from one of are first detected. Odonto hypophosphatasia his/her parents). In this form, mild HPP can In October 2015, a new treatment was refers to children and adults who have only occur from generation-to-generation. The introduced in the form of the targeted enzyme dental, but not skeletal problems (premature loss perinatal form of HPP can often be detected replacement therapy Strensiq (asfotase alfa). of teeth). The x-ray changes are quite distinct to during pregnancy by ALP gene mutation Strensiq is a tissue-nonspecific alkaline the trained eye. Similarly, the diagnosis of HPP analysis. Individuals with HPP and parents of phosphatase indicated for the treatment of is largely substantiated by measuring ALP in the children with HPP are encouraged to seek perinatal, infantile, and juvenile-onset hypophosphatasia (HPP), and works by replacing alkaline phosphatase. Since it’s approval, many Hypophosphatasia of our families have chosen to begin this therapy. Contributing Authors: Careful consideration and consultation with a physician knowledgeable about this treatment, and the disorder hypophosphatasia itself, is recommended before starting this therapy. We have many resources available to patients and Michael P. Whyte, M.D. providers who are considering starting this drug Medical Director M to treat their hypophosphatasia. Please see the Center for resources section below for general MAGIC and Molecular Research information, and additional resources regarding MAGIC hypophosphatasia and it’s treatment with Shriners Hospital The Foundation® Strensiq. St. Louis, Missouri For Children’s Growth

Many resources are available for families and their physicians on MAGIC's website, Not an illusion or magical, www.magicfoundation.org, such as But the caring for children The MAGIC Foundation is a national nonprofit and their families  Downloadable HPP brochure organization created to provide support services  Patient information for drug Strensiq for the families of children afflicted with a wide * * * *  Physician information for drug Strensiq variety of chronic and/or critical disorders, Dedicated to the growth  Member benefits or to join MAGIC syndromes and diseases that affect a child’s and overall development  HPP Facebook group for Parents growth. Some of the diagnoses are quite common while others are very rare. Of children  HPP Facebook group for adults  Physician referrals or to speak to someone about HPP MAGIC Continues and develops through membership 4200 Cantera Dr. fees, corporate sponsorship, private donations Suite 106 and fundraising. Warrenville, IL 60555 This brochure is for informational purposes only. Neither The MAGIC Foundation nor the 630-836-8200 contributing physician assumes any liability for 630-836-8181 fax its content. Consult your physician for diagnosis and treatment. 800-3MAGIC3 www.magicfoundation.org

Revised 2016