What Is Hypophosphatasia?

Medically Reviewed by Renee A. Alli, MD on May 20, 2023
6 min read

Hypophosphatasia (HPP), also called Rathbun disease, is a rare condition you inherit from your parents. It keeps your bones and teeth from developing the right way, making them more likely to form incorrectly or to break.

HPP is caused by changes (mutations) in the DNA of a gene. Normally, your teeth and bones build themselves up with calcium and phosphorus (a process called mineralization) to get stronger. With HPP, mineralization doesn't work the way it should.  

Your body has checks and balances to make sure every process happens the way it’s supposed to. And too much mineralization is a bad thing if it happens in the wrong place, like your blood. So there are chemicals in your body that keep it in check.

But your body also makes an enzyme called alkaline phosphatase (ALP) that keeps these mineral-blocking chemicals from affecting your bones and teeth. This allows more mineralization in those spots, where it's needed.

When the gene that produces ALP is mutated, the enzyme can’t do its job. Mineral-blocking chemicals build up where they shouldn’t. That keeps minerals from getting into your bones, which makes them softer than normal.

HPP varies a lot from person to person. It can be mild, serious, or even fatal. This mostly depends on how much ALP enzyme you have in your body. Generally, the less you have, the worse your HPP.

It can show up anytime from infancy to adulthood. The most common form, called the “odonto” form, makes you lose your baby teeth too early but doesn’t affect your bones. This kind of HPP often goes undiagnosed.

The most serious and rarest form, called perinatal HPP, shows up around the time you’re born. It's almost always fatal without treatment. But in another type, benign prenatal, bone problems that a doctor can see on an ultrasound get better on their own soon after the baby is born.

Sometimes, people are genetic “carriers” of HPP, but don’t have any symptoms. These people can pass HPP to their children.

Symptoms of HPP vary widely, but can include:

  • Bowed (curved) arms and legs
  • Short stature
  • In babies, failure to grow or gain weight as they should
  • Fused skull bones. This can cause high fluid pressure in the brain, leading to headaches and bulging eyes.
  • Soft, weak, or deformed bones, also called rickets (vitamin D deficiency)
  • Wider than normal wrist and ankle bones
  • Breathing issues due to problems with chest and rib bones
  • Painful bones and joints
  • Poor muscle tone (hypotonia) that makes babies seem “floppy”
  • High levels of calcium in the blood, which can lead to vomiting, constipation, weakness, and kidney damage
  • Seizures
  • Teeth that fall out before age 5, or unexpected tooth loss at any age
  • Problems walking
  • Bone fractures early on, especially in the feet and legs, that may be slow to heal
  • Sudden, serious arthritis

Many adults with HPP will remember having symptoms growing up, but never got a diagnosis as children.

If you or your child have symptoms of HPP, your doctor will ask about your family history and do a thorough exam. It will include x-rays and blood tests.

If they suspect HPP, they can do a genetic test to see whether you or your child have mutations in the ALP-producing gene. But this test isn’t widely available and can be expensive. Fortunately,  doctors can often diagnose HPP with other tests.

Sometimes, your doctor suspects HPP after they find abnormal enzyme levels during a routine blood test. They'll do follow-up tests, and look at things like age and family history, to confirm an HPP diagnosis.

If you suspect HPP, you can ask to be tested for low ALP. Keep in mind, though, that other, more common conditions can also cause abnormal enzyme levels.

Because most doctors are not HPP specialists, some families face frustrating delays in getting diagnosed. If you inform yourself about the causes and signs of HPP,  you can discuss your concerns with your doctor knowledgeably and help them figure out what's causing the symptoms.

When seeking an HPP diagnosis or treatment, describe your symptoms (or your child's) in as much detail as possible. If you can, tell them exactly where the pain is and how long the symptoms have lasted. Questions you could ask include:

  • Should I (or my child) get a blood test?
  • What other tests do you recommend?
  • Based on the symptoms, do you think it could be HPP? If not, why?
  • What are the treatment options?
  • Do these have any side effects?
  • How much do they cost, and are there financial assistance programs?
  • How often will I (or my child) need to come in?
  • Can you recommend a bone disease specialist?
  • What kind of exercise can be done safely?
  • Are there devices that might help, like braces or a walker?
  • Are there any clinical trials that could help?
  • What’s the prognosis for me (or my child)?

To get the most out of your visits, don’t be afraid to ask lots of questions. Ask your doctor to clarify anything you don’t understand. Keep a record of symptoms, tests, and surgeries. Ask your doctor if you can record your talks, or take notes on your phone or on paper. You could also bring along someone along who can do that for you.

Doctors use a drug called asfotase alfa (Strensiq) to treat HPP that starts in infancy or childhood. You get it as a shot under your skin. It replaces the ALP in your bones.

In addition to taking asfotase alta, you or your child will have a care team who will come up with other treatments and lifestyle changes to help with symptoms. These might include:

  • Nonsteroidal anti-inflammatory drugs, or NSAIDs, like ibuprofen (Advil) or acetaminophen (Tylenol) for bone or joint pain
  • Surgery on the skull or a shunt to ease pressure on the brain
  • Vitamin B6, which can help control seizures in some cases
  • Lowering calcium in your blood, by restricting your diet or getting injections of calcitonin, a hormone that regulates calcium levels
  • Regular dental care
  • Physical therapy
  • Inserting metal rods into bones that frequently break
  • Using a foot orthotic device or “boot”
  • Avoiding bisphosphonate drugs, used to treat other bone disorders such as osteoporosis, since they can make HPP worse

There are also a few experimental treatments for HPP. One is a drug called teriparatide. It's sometimes used “off-label” to help heal small stress fractures in the feet of people with HPP, but doctors can't use it in children. Doctors can also use bone marrow and stem cell transplants to treat serious HPP.

Clinical trials are studies that look at possible new treatments for diseases. Ask your doctor if one might be right for you.

Asfotase alta can be effective, but it can also be expensive. Talk with your doctor about the costs and benefits of taking it. If your symptoms are mild, you may be able to manage them with other treatments. If your symptoms are more serious, ask your doctor and pharmacist whether discounts are available.

Bone fractures, pain, and other symptoms can make everyday life difficult. People with rare diseases often have to advocate for themselves, so inform yourself as much as possible about HPP. This will help you take an active role in your or your child’s healthcare.

Once you've figured out what your or your child’s physical limits are, respect them. Get comfortable with setting boundaries and giving yourself time to rest.

Your care team will probably include several specialists. It may include a pediatrician, surgeon, orthodontist, dentist, pain management expert, and physical therapist. Together, they'll work to treat your or your child's symptoms. If bone disorders run in your family, you may want to speak to a genetic counselor to discuss your risk of passing HPP to your child.

Several more common conditions have symptoms similar to those of HPP. Your doctor might suspect other bone, joint, or teeth problems, like osteoporosis, arthritis, rickets (vitamin D deficiency), or gum disease. If your doctor doesn't think you have HPP, but their diagnosis doesn’t seem to fit, don't be afraid to get a second opinion. It’s OK to ask for a referral to a specialist.

HPP can have lasting effects on growth and quality of life, especially for people who have it during childhood. Treatment often takes several years. But over time it can improve symptoms significantly, even in life-threatening cases.

Support and advocacy groups can help you connect with others living with HPP. Talk with your doctor or go online to research these groups, which are listed on the National Institutes of Health (NIH) website.

Visit the National Organization for Rare Disorders (NORD) website to find assistance programs meant for people with HPP. These can help you cover expenses like travel to see specialists or out-of-pocket insurance costs.

You can also connect with other families living with hypophosphatasia in groups hosted on social media platforms like Facebook. These families can give you tried-and-true ideas for making life easier for you and your child.