About Hypophosphatasia

The signs and symptoms of HPP vary considerably, ranging from stillbirth caused by a complete lack of skeletal mineralization to relatively simple problems with tooth development. In general, the earlier in life symptoms begin, the more severe those symptoms can be over time.

Although HPP spans a great range of severity, all of those affected experience common underlying bone problems across all ages. At least six clinical forms of HPP have been described in the medical literature, classified according to the age at which symptoms first appear.

Learn more about the about the clinical forms of HPP.

HPP in the Perinatal Period

• Most severe form
• Profound skeletal hypomineralization may result in deformed limbs or a complete lack of skeletal formation
• Respiratory difficulties due to under-mineralized ribs
• Long-term survival is very rare; stillbirth is common

HPP in the Infantile Period

Onset occurs between birth and six months of age Inadequate weight gain and failure to thrive Deformed or shortened limbs Soft skull Respiratory compromise due to under-mineralized ribs Vitamin B6-responsive seizures Increased levels of calcium in blood (hypercalcemia) and urine (hypercalciuria) can lead to renal compromise and episodes of recurrent vomiting Mortality is approximately 50 percent

X-ray image of infant with hypophosphatasia

HPP in the Childhood Years

• Premature loss of baby teeth, before age 5
• Delayed walking
• Rickets (under-mineralized and deformed bones resulting in short stature, bowed long bones, knock knees)
• Hypermobile joints
• Waddling gait
• Bone pain
• Fractures are common

HPP in Adults

Under-mineralized, “soft” bones known as osteomalacia Recurring fractures in feet and partial fractures in the thighs and hips, causing chronic pain Premature loss of adult teeth May suffer from pseudogout (sudden, severe pain in joints caused by crystals in the joint lining) History of mild rickets, premature loss of baby teeth, and other dental problems

Pseudogout

Odontohypophosphatasia

• Mildest form of HPP
• Dental disease is only apparent clinical abnormality
• Premature loss of baby teeth
• May explain some cases of “early-onset periodontitis”

Benign in utero HPP

• Mild form of HPP
• Bowing of major long bones observed by sonography, but does not worsen at birth or lead to respiratory compromise
• Spontaneous improvement may occur and patients subsequently experience a milder form of HPP (similar to childhood HPP)