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What is Hypophosphatasia?

Hypophosphatasia (HPP) is a rare genetic disorder that affects bone and tooth development. The disorder causes defective mineralization. Mineralization is the process through which calcium and phosphorus are deposited in developing bones and teeth. In HPP a person’s bones are soft and prone to fracture and deformity. A person may also experience premature tooth loss.

HPP affects all ages. It can be severe and life-threatening, especially surrounding birth, but many experiences milder forms of the disease.

There are six main types of HPP:

  • Benign prenatal HPP
  • Lethal perinatal HPP
  • Infantile HPP
  • Childhood HPP
  • Adult HPP
  • Odontohypophosphatasia

Causes of Hypophosphatasia

Hypophosphatasia is caused by mutations within the ALPL gene. This gene provides instructions for making an enzyme called alkaline phosphatase, which plays an essential role in mineral building and retention in the bones and teeth. Mutations in this gene lead to an abnormal version of the enzyme, promoting defective bones and teeth.

Risk Factors of Hypophosphatasia

You are at risk for hypophosphatasia under the following conditions:

  • One or both of your parents carries a mutated ALPL gene.
  • You inherited two copies of the mutated gene from your parents (severe HPP)
  • You inherited only one mutated copy, from only one parent (mild HPP).

Symptoms of Hypophosphatasia

Symptoms vary widely and may appear any time from before birth to adulthood. Some children will develop severe complications early, whereas others may experience a milder form which improves with age.

Perinatal HPP symptoms include skeletal abnormalities, including deformities of the chest wall, short legs, bowed legs, or both.

For infants, symptoms include:

  • Failure to grow at the expected rate
  • Abnormally short limbs
  • Chest abnormalities
  • Abnormally soft skull bones

Symptoms of childhood cases can include:

  • Decreased mobility
  • Skeletal malformations
  • Bone and joint pain
  • Enlarged wrist or ankle joints
  • Abnormal skull shape
  • Early loss of baby teeth
  • Short stature with bowed legs or knock knees

Symptoms of adult HPP include:

  • Softening of the bones
  • Foot and thigh bone fractures
  • Premature loss of adult teeth
  • Joint pain and inflammation

Diagnosis of Hypophosphatasia

Your doctor diagnoses HPP based on your signs and symptoms, medical history, physical examination, and lab tests. Tests may include X-rays and biochemical tests that measure the activity of alkaline phosphatase in the blood.

During pregnancy, chorionic villus sampling (CVS) is used to check for ALPL gene mutations. Odontohypophosphatasia is often diagnosed when there are dental abnormalities, including premature tooth loss, but no other skeletal disease.

Treatment for Hypophosphatasia

An alkaline phosphatase enzyme replacement therapy (ERT) is used to treat perinatal, infantile, and juvenile-onset HPP. Infants treated with ERT can experience significant improvement of respiratory function, skeletal mineralization, and reduced mortality.

In adults with HPP, a man-made form of parathyroid hormone used to treat osteoporosis has been shown to help in fracture-healing.

Other treatments that target specific symptoms and complications include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Vitamin B6 helpto control seizures in severely affected infants
  • Regular dental care
  • Physical and occupational therapy

Surgery may also be recommended. Adults affected by repeated fractures may undergo a procedure called rodding, in which a metal rod is placed through the middle of a bone to make it stronger and more stable. Children are sometimes given orthotic braces to encourage stability.