Diagnosis of Osteogenesis Imperfecta in Children
キーワード
概要
説明
Osteogenesis imperfecta is a genetic disorder of the connective tissue matrix caused by abnormal collagen microfibril assembly, .Several clinical subtypes of Osteogenesis imperfecta have been described based on the clinical, biochemical, and molecular nature of the disorder . New research is emphasizing the structural interaction within the microfibril and identifying regions within the collagen, which play greater or lesser roles in the structural properties of the triple helix, .In taking this information into account, clinical phenotypes resulting from certain mutations can be predicted because of this pathogenetic correlation.
The clinical manifestations vary considerably, ranging from a severe perinatal lethal form to a mild disorder which only becomes evident in adulthood, manifesting as premature osteoporosis, .Most commonly, however, Osteogenesis imperfecta presents in childhood with multiple fractures and related complications, .The precise incidence of Osteogenesis imperfecta is unknown and reports vary from approximately 1/100,000 to 1/25,000 dependent on the criterion used to define Osteogenesis imperfecta.
Severe forms and milder disease occur with approximately similar incidence. Severe and mild forms share the cardinal feature of bone fragility, which is characterized by bone fractures often after little or no trauma, .Several findings in Osteogenesis imperfecta are common to other disorders of connective tissues; hyper-mobile joints and a blue sclera are among these features frequently described, The incorporation of abnormal type 1 collagen in teeth results in brittle opalescent teeth, the hallmark of Dentinogenesis Imperfecta, often seen in Osteogenesis imperfecta, .Progressive conductive hearing loss in early adulthood is the result of damage to the ossicles in the middle ear; over time, hearing loss typically progresses and combined conductive and sensorineural hearing loss may be seen in adults, similar to that of otosclerosis. Short stature and bone deformity are common features of the disorder The mainstay of treatment is orthopedic management along with physiotherapy, Bisphosphonates are being evaluated for efficacy and clinical trials have shown improvement at least in bone mineral density
Disorders associated with fragility fractures in children:
A) Primary conditions
1. Genetic disorders :- Osteogenesis imperfecta - Ehlers-Danlos syndrome - Marfan syndrome Homocystinuria - Osteoporosis - Hypophosphatasia Polyostotic fibrous dysplasia - Rickets (genetic forms)
2. Idiopathic juvenile osteoporosis B) Secondary conditions
1- Chronic inflammatory conditions Systemic lupus erythematosus - Inflammatory bowel disease - Nephrotic syndrome 2- Reduced mobility Cerebral palsy - Duchenne muscular dystrophy - Posttraumatic 3- Infiltrative Leukemia - Thalassemia
4- Endocrine Hypogonadism - Growth hormone deficiency - Cushing syndrome Hyperthyroidism - Diabetes mellitus 5- Nutritional/malabsorptive Vitamin D deficiency - Celiac disease - Biliary atresia Cystic fibrosis - Anorexia nervosa 6- Renal Chronic kidney disease - Secondary hyperparathyroidism 7- Iatrogenic Glucocorticoids - Anticonvulsants - Methotrexate - Radiation therapy
日付
最終確認済み: | 04/30/2017 |
最初に提出された: | 05/24/2017 |
提出された推定登録数: | 05/24/2017 |
最初の投稿: | 05/29/2017 |
最終更新が送信されました: | 05/24/2017 |
最終更新日: | 05/29/2017 |
実際の研究開始日: | 05/31/2017 |
一次完了予定日: | 12/31/2018 |
研究完了予定日: | 02/28/2019 |
状態または病気
介入/治療
Drug: Repeated fractures group
段階
アームグループ
腕 | 介入/治療 |
---|---|
Repeated fractures group detection of gene mutations of osteogenesis imperfecta in single group of patients with repeated fractures then start treatment with zoledronic acid in doses children less than 5 years ( 0.025 milligram for each kilogram every 3 months for 18 months duration) children more than 5 years ( 0.05 milligram for each kilogram every 6 months for 18 months duration) | Drug: Repeated fractures group intravenous injections once every 3 months |
適格基準
研究の対象となる年齢 | 1 Month に 1 Month |
研究に適格な性別 | All |
サンプリング方法 | Non-Probability Sample |
健康なボランティアを受け入れる | はい |
基準 | Inclusion Criteria: 1. Positive family history of fractures or stillbirths. 2. Results of biochemical tests correlate with osteogenesis imperfecta. 3. Low bone density. Exclusion Criteria: 1. Presence of secondary causes of fractures. 2. Abnormalities of biochemical tests or hormonal profile. 3. Negative family history. 4. Fractures in same site each time. |
結果
主な結果の測定
1. Percentage of children diagnosed as osteogenesis imperfecta [1 month]