Natural History Study of Patients With Hypophosphatasia (HPP)
Natural History Study of Patients With Hypophosphatasia (HPP)
Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by defective bone
 and teeth mineralization caused by mutations of the ALPL gene, which encodes for the
 tissue-nonspecific alkaline phosphatase (TNSALP) isozyme, resulting in decreased serum and
 bone alkaline phosphatase levels. To date, over 250 different mutations in the gene encoding
 TNSALP have been associated with HPP. Clinically, the loss of TNSALP function results in
 progressive skeletal impact as well as progressive impact on all other major organ systems.
 It clinically manifests as rickets in infants and children and osteomalacia at all ages. The
 severe form of the disease has been estimated to have a prevalence of about 1 in every
 100,000 live births.
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.