Hypophosphatasia

Hypophosphatasia (HPP) is a rare genetic condition that affects how bones and teeth develop and stay strong. Normally, the body uses minerals like calcium and phosphorus to harden bones and teeth. With HPP, this mineralization process doesn’t work as it should. This can lead to soft bones that break easily, along with tooth loss or trouble chewing. Because it’s a metabolic bone disorder, HPP can affect people in different ways, ranging from life-threatening complications in infants to painful stress fractures in adults.

At the Penn Bone Center, endocrinology specialists treat all forms of HPP and other complex bone conditions. The team uses advanced diagnostics, including hypophosphatasia genetic testing, to confirm a diagnosis and create a tailored care plan. We’re dedicated to providing the latest treatments to help strengthen your bones and help you stay active.

HPP is usually grouped into types based on when symptoms begin and how severe they are. In general, earlier onset is linked to more severe disease.

The main types include:

• Perinatal: This is the most severe form and begins before birth.
• Infantile: Symptoms appear within the first six months of life.
• Childhood: This can range from mild to severe bone and growth issues.
• Adult: Often diagnosed later, this form typically includes bone pain and stress fractures.
• Odontohypophosphatasia: This mild form mainly affects the teeth.
• Pseudohypophosphatasia: A very rare form, this occurs when lab results look normal, but symptoms resemble the infantile form.

Because HPP affects the whole body, symptoms can vary based on the type of hypophosphatasia and when it begins. Some people have mild symptoms, while others have more serious complications that affect growth, breathing, or mobility.

Common hypophosphatasia symptoms include:

• Soft bones that break easily or heal slowly, especially in the feet
• Musculoskeletal pain or joint pain
• Short stature or delayed growth in children
• Early loss of baby teeth or loss of adult teeth not due to trauma
• Weak muscles or delayed walking
• Bowed legs or other changes in bone shape
• Calcium deposits in the kidneys, joints, or eyes

Hypophosphatasia is caused by changes in the ALPL gene. This gene provides instructions for making an enzyme, alkaline phosphatase, that helps harden bones and teeth. When the gene doesn’t work as expected, the mineralization process is disrupted. As a result, bones may remain soft and weak. At the same time, minerals like calcium can build up in other parts of the body, which might affect the kidneys, joints, or other tissues.

HPP is inherited, meaning it’s passed down in families. Some forms require a gene change from both parents, while others develop if only one parent carries the mutation. Severity often depends on how much the gene affects enzyme activity. Penn Medicine specialists can help you understand your family’s pattern through hypophosphatasia genetic testing.

There isn’t a cure for HPP, but treatment can help manage symptoms. For some people whose disease develops in childhood, treatment can include enzyme replacement therapy, an injection that improves bone mineralization.

Care is often coordinated across specialties to address the full range of symptoms. Supportive treatment may include:

• Medications to improve bone strength and fracture healing
• Care for fractures, like casting, bracing, or surgery when needed
• Physical therapy to improve strength, balance, and mobility
• Pain management for bone and joint discomfort
• Dental care to address early tooth loss and protect oral health
• Respiratory support for breathing complications
• Nutritional support to manage calcium levels in the blood
• Monitoring disease progression over time

Because hypophosphatasia is rare, it may not be recognized right away. At Penn Medicine, care is led by the Penn Bone Center, where specialists are experienced in diagnosing and treating this condition.

Experts from multiple specialties work together to manage all aspects of bone health. Your care team may include endocrinologists, orthopaedic specialists, dentists, rheumatologists, physical therapists, and others with experience in metabolic bone disease.

The team is also building a strong clinical and research program focused on hypophosphatasia, offering access to new therapies and clinical trials.