Natural History Study of Adult and Pediatric Patients With Hypophosphatasia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Medical History of HPP Patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Any patient without confirmation of clinical diagnosis of HPP.
研究组 & 干预措施
Medical History of HPP Patients
Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP.
结局指标
主要结局
Medical History of HPP Patients
时间窗: 100 years
Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP
次要结局
- long-term efficacy of treatment modalities(100 years)
- potential long term complications of the disease and/or treatment(100 years)
- quality of life issues for patients living with hypophosphatasia(100 years)