Natural History Study of Patients With Hypophosphatasia (HPP)

Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a
wide range of clinical expressivity, with a spectrum ranging from stillbirth without
mineralized bone to early loss of teeth without bone symptoms. Depending on the age at
diagnosis six clinical forms are currently recognized: perinatal (lethal), perinatal benign,
infantile, childhood, adult and odontohypophosphatasia. Severe forms of HPP (perinatal and
infantile) are inherited as an autosomal recessive trait and in milder forms (adult and
odontohypophosphatasia) autosomal recessive and autosomal dominant inheritance coexist.

Because of the rarity of HPP as well as the side spectrum of both clinical presentation and
inheritance patterns of the HPP trait, a natural history study cataloging specific clinical
data with HPP would prove invaluable for future research into this disease. Specifically, it
is our goal to create a comprehensive multi-discipline modality for care for hypophosphatasia
patients, researching clinical manifestations of the disease such as extent of bone disease,
ophthalmologic manifestations, orthopedic issues, renal issues, musculoskeletal
manifestations as well as other more anecdotal findings such as those seen with cochlear
implant failures and/or early menopause.

Inclusion Criteria:

- Patients or their legal representative must provide written informed consent or, if
applicable, qualify for waiver of consent.

- Patients must have a pre-established clinical diagnosis of HPP, as indicated by one or
more of the following:

- Serum alkaline phosphatase (ALP) below the age-adjusted normal range

- Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered
for at least 1 week prior to determination)

- Evidence of osteopenia or osteomalacia on skeletal radiographs

- Genetic analysis fof the ALPL gene

Exclusion Criteria:

- Any patient without confirmation of clinical diagnosis of HPP.