What Is Hypophosphatasia? Symptoms, Causes, Diagnosis, Treatment, and Prevention

Hypophosphatasia (HPP) is a rare inherited disorder that affects the development of bones and teeth.

The disorder affects mineralization — the process through which calcium and phosphorus are deposited in developing bones and teeth. HPP causes defective mineralization, which means that instead of teeth and bones that are strong and rigid, a person’s bones are soft and prone to fracture and deformity. A person may also experience premature tooth loss.

HPP affects infants, children, and adults. It can be severe and life-threatening, especially before birth and just after it, but many experience milder forms of the disease.

Rickets, a bone disorder that affects children, produces many of the same symptoms, but it’s usually not inherited and is caused by a lack of calcium and vitamin D. (There is an inherited form of rickets, but it is very rare.)

There are six main types of HPP. They are:

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

In benign prenatal HPP, an unborn infant may present with skeletal defects that will resolve into a less severe form of HPP. Lethal perinatal HPP results in death, either in the womb or by stillbirth. Odontohypophosphatasia, which only affects the teeth, is the mildest form of the condition.

Symptoms of childhood cases vary but may include:

• Short stature with bowed legs or knock knees
• Decreased mobility
• Skeletal malformations
• Bone and joint pain
• Enlarged wrist or ankle joints
• Abnormal skull shape
• Losing baby teeth earlier than usual with the root still intact

• Softening of the bones
• Frequent fractures of the foot and thigh bones
• Premature loss of teeth
• Joint pain and inflammation

Odontohypophosphatasia is characterized by the premature loss of baby teeth in childhood or premature loss of teeth in adulthood. With this form of HPP, there are no symptoms that affect or involve the bones.

Ultrasounds during pregnancy may also show short and bowed long bones.

Prognosis of Hypophosphatasia

Hypophosphatasia is a lifelong disease.

Strensiq is used to treat perinatal, infantile, and juvenile onset HPP.

Other treatments target specific symptoms and complications.

These treatments include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) to treat bone and joint pain
• Vitamin B6 to help to control seizures in severely affected infants
• Regular dental care beginning early on
• Physical and occupational therapy

Surgery may also be recommended. Adults suffering from repeated fractures may undergo a procedure called rodding, in which an orthopedic surgeon places a metal rod through the center opening of a bone to make it stronger and more stable.

Children may be given orthotic braces to encourage stability, and in-sole orthotics may be used by both adults and children.

Related: What to Eat — and Avoid — for Strong Bones if You Have Ankylosing Spondylitis

Prevention of Hypophosphatasia

Hypophosphatasia cannot be prevented, but treatments such as the ones outlined above are available to help manage the symptoms.

In addition to failure to gain weight, the following complications in infancy include:

• Respiratory problems, including a predisposition to pneumonia
• Hypercalcemia, or high levels of calcium in the blood
• Increased intracranial pressure caused by craniosynostosis (the premature closure of one or more of the joints that connect the bones of a baby’s skull)
• Nephrocalcinosis, a disorder that occurs when too much calcium is deposited in the kidneys, is another possible complication.

Complications in adults with HPP include chronic pain of the bones, joints, and muscles.

They may also lose their secondary (adult) teeth prematurely.

A wide variety of disorders may have some symptoms that are similar to those of HPP.

• Osteogenesis Imperfecta (OI) This is a group of rare disorders affecting connective tissues and characterized by brittle and fragile bones that fracture easily.
• Rickets As mentioned earlier, this bone disorder can be caused by genetic inheritance or by calcium and vitamin D deficiencies, a lack of sun exposure, or maternal malabsorption of those nutrients during pregnancy.
• Campomelic Dysplasia This rare genetic disorder affects the development of the skeleton, the reproductive system, and the face. It develops before birth, and children born with the disorder rarely survive past infancy.

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• Achondrogenesis A group of severe disorders, present from birth, that affect the development of cartilage and bone. Most infants with achondrogenesis have severely underdeveloped lungs, and most die before or shortly after birth.

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