Duke University
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 domi…
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 * Must be current patient in t…
Arctuva estimate
Verify or correct the compensation shown for this listing.