Natural History Study of Patients With Hypophosphatasia (HPP)

Official title

Natural History Study of Adult and Pediatric Patients With Hypophosphatasia

Overview

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.

Detailed description

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.

Primary outcome measures

• Medical History of HPP Patients [Time frame: 100 years]

Secondary outcome measures (3)

• long-term efficacy of treatment modalities [Time frame: 100 years]
• potential long term complications of the disease and/or treatment [Time frame: 100 years]
• quality of life issues for patients living with hypophosphatasia [Time frame: 100 years]

Eligibility criteria

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 the Duke University System.

Exclusion criteria

• Any patient without confirmation of clinical diagnosis of HPP.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Family-based

Study locations

United States · 1 center

• Duke University Medical Center — Durham

Identifiers

NCT: NCT02237625 · Pro00049204 · Pro00049204

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗