Hypophosphatasia is an inherited metabolic (chemical) bone disease that results from low levels of an enzyme called alkaline phosphatase (ALP). Enzymes are proteins that act in the body's chemical reactions by breaking down other chemicals. ALP is normally present in large amounts in bone and liver. In hypophosphatasia, abnormalities in the gene that makes ALP lead to production of inactive ALP. Subsequently, several chemicals -including phosphoethanolamine, pyridoxal 5'-phosphate (a form of vitamin B6) and inorganic pyrophosphate - accumulate in the body and are found in large amounts in the blood and urine of people with Hypophosphatasia. It appears that the accumulation of inorganic pyrophosphate is the cause of the characteristic defective calcification of bones in infants and children (rickets) and in adults (osteomalacia). Nevertheless, the severity of hypophosphatasia is remarkably variable from patient-to-patient.

Symptoms & Diagnosis


The most severely affected fail to form a skeleton in the womb and are stillborn. The most mildly affected patients may show only low levels of ALP in the blood, yet never suffer bony problems. In general, patients are categorized as having "perinatal", "childhood" or "adult" hypophosphatasia depending on the severity of the disease, which in turn is reflected by the age at which bony manifestations are first detected. Odontohypophosphatasia refers to children and adults who have only dental, but not skeletal, problems (premature loss of teeth). The x-ray changes are quite distinct to the trained eye. Similarly, the diagnosis of hypophosphatasia is largely substantiated by measuring ALP in the blood (a routine test) that is low in Hypophosphatasia. However, it is important that the doctors use appropriate age ranges for normals when interpreting an ALP level. 




It has been estimated that severe forms of hypophosphatasia occur in approximately one per 100,000 live births. The more mild childhood and adult forms are probably somewhat more common. About one out of every 200 individuals in the United States may be a carrier for hypophosphatasia.


Depending on the severity of the skeletal disease, there may be deformity of the limbs and chest. Pneumonia can result if chest distortion is severe. Recurrent fractures can occur. Teeth may be lost prematurely, have wide pulp (inside) chambers, and thereby be predisposed to cavities.


Inheritance Factors


The severe perinatal and infantile forms of hypophosphatasia are inherited as autosomal recessive conditions. 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 and odonto hypophosphatasia 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. The perinatal form of hypophosphatasia can often be detected during pregnancy by ultrasound and by measuring ALP activity in chorionic villus samples from amniocentesis. Individuals with hypophosphatasia and parents of children with hypophosphatasia are encouraged to seek genetic counseling to explain the likelihood and severity of hypophosphatasia recurring in their families.

(chart can be found at hypophosphatasia.com/hcp)

(chart can be found at hypophosphatasia.com/hcp)




Prognosis The outcome following a diagnosis of hypophosphatasia is very variable. In general, the earlier the diagnosis is made the more severe the skeletal manifestations. Cases detected in the womb or with severe deformity at birth almost always have a lethal outcome within days or weeks. When the diagnosis is made before six months of age, some infants have a downhill and fatal course, others survive and may even do well. When diagnosed during childhood, there can by presence or absence of skeletal deformity from underlying rickets, but premature loss of teeth (less than five years of age) is the most common manifestation. Adults may be troubled by recurrent fractures in their feet and painful, partial fractures in their thigh bones.




For many years, treatment has been generally directed toward preventing or correcting the symptoms or complications. Procedures such as rodding, especially in adults, can be helpful with painful partial fractures in their thigh bones. Expert dental care and physical therapy are recommended. Monitoring levels such as alkaline phosphatase, B6, and calcium (which are/can be outside the limits of normal in hypophosphatasia) should be undertaken and are dependent upon how the patient is being treated.


In October 2015, a new treatment was introduced in the form of the targeted enzyme replacement therapy Strensiq (asfotase alfa). Strensiq is a tissue-nonspecific alkaline phosphatase indicated for the treatment of perinatal, infantile, and juvenile-onset hypophosphatasia (HPP), and works by replacing alkaline phosphatase. Since it’s approval, many of our families have chosen to begin this therapy. 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 providers who are considering starting this drug to treat their hypophosphatasia. Please see the resources section below for general MAGIC information, and additional resources regarding hypophosphatasia and it’s treatment with Strensiq.


Contributing Authors:

Michael P. Whyte. M.D.
Medical Director, Metabolic Research Unit
Shriners Hospital, St. Louis, Missouri


Tracey Porreca
Hypophosphatasia Division Consultant
The MAGIC Foundation



A Personal Story

Hello! My name is Tracey Porreca and I am the Division Consultant for The MAGIC Foundation. Over 20 years ago when my son was diagnosed with Hypophosphatasia, The MAGIC Foundation helped start the first support group in the world for this disorder. My daughter and I were also diagnosed and at that time, I was able to network with many families, and we even had a couple of meet and greets at MAGIC’s Annual Educational Conference. Life takes many twists and turns and I had to step away for several years, but MAGIC has always been here, ready to serve the families in the Hypophosphatasia community. My children are grown now and with renewed energy, I’m happy to be back to support and network families. The MAGIC Foundation has so much to offer both children and adults, and I’m excited to see where this next part of the journey takes all of us. Please look over the materials enclosed and if you have any questions or would like to speak with me directly, please don’t hesitate to contact MAGIC. We’re here to help and support you in this journey!


My story is a bit long, but I hope it’s a good one. It starts back in 1991 when my youngest child of 3, a son, was born. Because he was my third child, I knew something wasn’t quite right. I remember commenting to someone how tiny his face appeared. I guess I shouldn’t be surprised that nurses and doctors looked at me somewhat quizzically, as shouldn’t all babies have tiny faces? It was just one thing I noticed which was a little different than my other two children. He seemed to lack some vigor and tone, but this was all dismissed and we went home a day after he was born. By the time he was 48 hours old, however, I had him in the pediatrician’s office for evening urgent appointments.


Something wasn’t quite right. He did not seem interested in nursing. He slept way too much. The soft spot in the top of his head was huge. These things just didn’t add up. He was examined and weighed. He had lost more than half a pound since birth. Not much more than to be expected, but enough for the pediatrician to ask me to bring him back again in a couple of days. I brought him back and by this time he had lost nearly a pound. More lethargic and less interested in nursing, it was decided we would try supplementing with formula. A recheck at one week revealed he had lost a full pound. At 9 days he was admitted to the hospital with a weight loss of nearly 1.5 pounds. Much testing was done – lab work, x-rays, examinations. His sodium was way too low, his potassium was way too high, and his bones appeared transparent on x-ray. More extensive testing was done and at a little over 2 weeks of age it was confirmed that my son had a rare form of Congenital Adrenal Hyperplasia (CAH).


Over the next month, his medical team discovered many things that did not fit with the CAH diagnosis. Most kids with CAH have an advanced bone age, but my son’s bones were more cartilage than bone. His head ballooned as he rehydrated and he developed communicating hydrocephalus. He had unusual kidney findings and was diagnosed with renal tubular acidosis. He was severely hypotonic and floppy, which should have resolved with rehydration and supplementation. Something else was amiss, but doctors were unable to figure out what. They chalked it all up to the rare form of CAH he had and at 6 weeks of age, he came home on 13 medications and a laundry list of specialty appointments. Thus began a very long journey of discovery.


Every time my child saw a specialist – endocrinology, neurology, rheumatology, hematology, nephrology, orthopedic – they seemed to find something new, and he would receive an additional diagnosis. They were treating the symptoms but I couldn’t help but feel this was masking a bigger issue. Keep in mind – this was 1991 and the internet barely existed. I didn’t have all the resources many families have now, but I was able to find out about The MAGIC Foundation who had a support group for families of children with CAH. I started networking with other families and it was a wonderful resource.

During this time, the doctors continued to try and figure out why the puzzle pieces didn’t quite fit. After receiving diagnoses of Ehlers-Danlos Syndrome, Robinow Syndrome, and Osteogenesis Imperfecta, a geneticist said to me “you know, he’s not typical for this disorder, but he’s definitely not typical for anything – let’s look at Hypophosphatasia.” I was able to find out about Dr. Michael Whyte at the St. Louis Shriner’s Hospital. Although my geneticist was less than enthusiastic, he agreed to send medical records and findings to Dr. Whyte and we made an appointment.


After being evaluated in the fall of 1993, it was confirmed that my son did indeed have Hypophosphatasia. Although still not a typical case, it seemed to fill in a lot of the gaps. It appears my son may have had CAH, but now also carried the diagnosis of Hypophosphatasia. The rest of the family was tested and I and my daughter both have the disorder. I talked to the folks at Shriners, and tried to find a support group for this disorder, but it just didn’t exist. I explained my situation to Mary Andrews at MAGIC and she agreed to help start something for Hypophosphatasia families through MAGIC. We immediately set to work to identify and network families.


Several years went by and we were on a roll. Families were networking, MAGIC was growing and we had a couple of meet and greets and even participated in a full conference with MAGIC. Dr. Whyte came and spoke. Unfortunately, as is all too common in families who have a child with special needs, this took a toll on my marriage and I ended up divorcing and becoming a single mom. I continued to network families through MAGIC but it became increasingly difficult for me personally to continue so I stepped back, even though MAGIC never left the side of the Hypophosphatasia community.


It’s now over 20 years later. My son has been doing remarkably well and is in that “honeymoon” period we sometimes hear about with these kids where their symptoms abate somewhat in puberty and young adulthood. He still had difficulty with work, fatigue, and generalized pain and weakness. My daughter, who actually did quite well as a youngster, has continued to have more and more difficulty. At the age of 30, she has had several fractures and has a lot of difficulty with her teeth. I’m just over 50 and the last couple of years have been difficult. I had femoral rodding surgery a few years back, have had multiple foot fractures, knee surgeries, and most recently dental reconstruction.


Over the past several years, a new drug has been trialed and was approved for perinatal, infantile, and juvenile onset hypophosphatasia. My children obviously had onset of symptoms in infancy or childhood, and my history has shown I did as well. I had difficulty walking as a child, as well as early tooth loss at the age of 2, along with other symptoms. My son and I consulted a nephrologist familiar with hypophosphatasia and started the new therapy Strensiq (asfotase alfa) at the beginning of 2016. My son has had amazing results. He has increases strength and energy. Both our labs have come back very encouraging. Time will tell how much improvement there is in the future, but as a mom, I couldn’t be more pleased. I would encourage anyone with hypophosphatasia to have a conversation about this new therapy. You and your provider can determine the best course.


And my personal life couldn’t be better. Just over 10 years ago I accepted a job in Alaska and moved here. I met and married the love of my life. He is very supportive and always there when I need him. We live in a remote area of Alaska, in a small cabin, with two dogs, and I love it. I’m now able to pursue my first love, photography, and have started a freelance photography business. And, I’m so happy to say, I’m back with The MAGIC Foundation. We are stepping up our outreach and networking efforts. MAGIC has many resources and can do so much for families who are affected by so many different disorders. They have a wonderful staff and supportive Division Consultants who are here to help. Their educational and support programs can’t be beat. If you have a question or a need, don’t hesitate to contact us. I am looking forward to once again working with families to provide them with the support they need. Thank you so much for taking the time to read this, and please don’t hesitate to contact myself or MAGIC if you have any questions.



»  Download a printable version of the Hypophosphatasia brochure
»  Patient information for the drug Strensiq
»  Physician information for the drug Strensiq
»  Click here for the link to a journal article discussing recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment with Strensiq (asfotase alfa).
»  Helpful information about Applying for Disability Benefits with an Endocrine Related Disorder - PEDIATRIC Patients
»  Helpful information about Applying for Disability Benefits with an Endocrine Related Disorder - ADULT patients
»  Click here for member benefits or to join The MAGIC Foundation
»  "LIKE" The MAGIC Foundation's Facebook page
»  If you are the parent of a child with HPP, join our closed HPP Facebook group for Parents
»  If you are an adult with HPP, join our closed HPP Facebook group for adults
»  After you request to join either Facebook group, please message an admin to gain access or email Tracey at hpp@magicfoundation.org
»  Click here for TSA guidelines on flying with medical conditions. It covers injectable medications, traveling with medical devices such as wheelchair, crutches, etc., and service dog rules.
»  Would you like assistance finding a physician experienced in HPP? Would you like to speak to someone about Hypophosphatasia? If so, call The MAGIC Foundation at 800-3MAGIC3 or (630) 836-8200 or Email Us

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