Clinical Trial: Natural History Study of Patients With Hypophosphatasia (HPP)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Natural History Study of Adult and Pediatric Patients With Hypophosphatasia

Brief Summary: 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 Summary:

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.


Sponsor: Duke University

Current Primary Outcome: Medical History of HPP Patients [ Time Frame: 100 years ]

Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: Duke University

Dates:
Date Received: September 9, 2014
Date Started: September 2014
Date Completion: September 2026
Last Updated: January 5, 2017
Last Verified: January 2017