A Rare, Inherited Metabolic Disorder That Affects Bones and Teeth 

Typically, a process called mineralization, or calcification, deposits calcium and phosphorus to form our bones and teeth, making them strong and hard. In people with hypophosphatasia (HPP), a genetic mutation causes a defect in the mineralization process. Not enough phosphorous and calcium are deposited in bones, making them soft and weak. This also makes bones more likely to develop deformities and fractures.

Symptoms, Diagnosis and Outlook

HPP can vary widely in its presentation among individuals. In more severe cases, the condition may be diagnosed before or shortly after birth. Sometimes, symptoms may not appear until adolescence or adulthood.

Symptoms of HPP in infancy may include:

• Short, bowed arms and legs
• Abnormally shaped chest/underdeveloped ribs or bones
• Soft skull bones
• Difficulty feeding
• Failure to thrive
• Respiratory problems, sometimes requiring mechanical ventilation
• High levels of calcium in the blood
• Vitamin B6-dependent seizures

Symptoms of HPP in adolescence may include:

• Early nontraumatic loss of baby teeth or adult (secondary) teeth with root intact
• Short stature/skeletal deformities
• Bowed legs 
• Knock knees
• Enlarged wrist and ankle joints
• Bone and/or joint pain
• Fractures
• Abnormal skull shape
• Gait or mobility issues
• Depression, anxiety or insomnia

Symptoms of HPP in adults may include:

• Softening of bones (osteomalacia)
• Increased fractures, especially in areas like feet and thighs (may be nontraumatic)
• Chronic bone and/or muscle pain
• Loss of adult (secondary) teeth
• Joint pain and inflammation
• Poor mobility
• Abnormal gait

Diagnosis of HPP is important so treatment can begin as early as possible. A doctor may order lab tests if certain characteristics and symptoms are present. Tests can include X-rays and biochemical tests, such as an alkaline phosphatase (ALP) test. Low levels of ALP may suggest HPP. Genetic testing may also be recommended.

The prognosis for HPP depends on the severity of the disease. HPP diagnosed during pregnancy or shortly after birth can be fatal if not treated immediately. Fortunately, the development of enzyme replacement therapy has led to promising results, including improved respiratory function and reduced mortality.

HPP diagnosed in adolescence and adulthood tends to be less severe but can progress over a lifetime and needs close monitoring. Treatment should be determined by your health care provider and can include enzyme replacement therapy, regular dental care and/or physical and occupational therapy.

Related Services and Treatments

• Orthopedics
• Orthopedics (Pediatric)
• Penn State Bone and Joint Institute
• Endocrinology
• Genetics
• Rheumatology
• Physical Therapy
• Occupational Therapy

Why Choose Penn State Health for Care

Top-Ranked by U.S. News & World Report

Penn State Health includes the Milton S. Hershey Medical Center, ranked as one of the best orthopedic providers in the country by U.S. News & World Report. This honor was earned because our doctors consistently deliver exceptional patient care and outcomes through their commitment to advanced treatments, translational research and provider training.

Advancing orthopedic medicine through research

The doctors and researchers in the Center for Orthopaedic Research and Translational Science at the Milton S. Hershey Medical Center are committed to advancing their field through scientific discovery and education. As the only locally based academic medical center in central Pennsylvania, Hershey Medical Center is a national leader in research and on the leading edge of new treatment options, including clinical trials, in partnership with Penn State College of Medicine.

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