Juvenile paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation.
Juvenile paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation.
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DOI：
10.1002/jbmr.1868
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发表时间：
2013-06
影响因子：
6.2
通讯作者：
Whyte, Michael P.
中科院分区：
文献类型：
--
作者：
Saki, Forough;Karamizadeh, Zohreh;Nasirabadi, Shiva;Mumm, Steven;McAlister, William H.;Whyte, Michael P.
关键词：
幼年型佩吉特病（JPD）是一种罕见的遗传性骨病，其生化特征是由于全身性骨骼更新加速引起血清碱性磷酸酶（ALP）活性显著升高。受影响的婴儿和儿童通常遭受骨痛和骨折和畸形，耳聋，并有巨颅。有些人存活到年轻的成年生活发展失明的视网膜病变所产生的血管微钙化。大多数JPD病例是由骨保护素（OPG）缺乏引起的，这是由于编码OPG的TNFRSF11B基因内的纯合功能丧失突变引起的。我们报告一个3岁的伊朗女孩与JPD和颅缝早闭谁有维生素D缺乏症在婴儿期。她在出生后第一年出现骨折，随后出现骨畸形、发育迟缓、发育不良和肺炎。在1岁时，血清生化研究表明，显着的高磷酸酶血症，以及低正常钙和低无机磷酸盐和25-羟基维生素D水平。这个近亲家族的前几代家庭成员也可能患有JPD和维生素D缺乏症。突变分析显示TNFRSF11 B中一个独特的错义改变（c.130 T> C，p.Cys44 Arg）的纯合性，该错义改变会损害OPG的富含半胱氨酸的结构域，该结构域结合NF-κ B受体激活剂配体（RANKL）。双亲均为该突变的杂合子。患者血清OPG水平极低，RANKL水平显著升高。她对快速口服维生素D补充后静脉注射帕米膦酸盐治疗反应良好。我们的病人是第一个被报道患有JPD的伊朗人。她的TNFRSF11B新突变加上婴儿期维生素D缺乏症与严重的JPD有关，这种JPD独特地并发于颅缝早闭。帕米膦酸盐治疗与维生素D充足可以有效治疗由OPG缺乏型JPD引起的骨骼疾病。
Juvenile Paget’s disease (JPD) is a rare heritable osteopathy characterized biochemically by markedly increased serum alkaline phosphatase (ALP) activity emanating from generalized acceleration of skeletal turnover. Affected infants and children typically suffer bone pain and fractures and deformities, become deaf, and have macrocranium. Some who survive to young adult life develop blindness from retinopathy engendered by vascular microcalcification. Most cases of JPD are caused by osteoprotegerin (OPG) deficiency due to homozygous loss-of-function mutations within the TNFRSF11B gene that encodes OPG. We report a 3-year-old Iranian girl with JPD and craniosynostosis who had vitamin D deficiency in infancy. She presented with fractures during the first year-of-life followed by bone deformities, delayed development, failure-to-thrive, and pneumonias. At 1 year-of-age, biochemical studies of serum revealed marked hyperphosphatasemia together with low-normal calcium and low inorganic phosphate and 25-hydroxyvitamin D levels. Several family members in previous generations of this consanguineous kindred may also have had JPD and vitamin D deficiency. Mutation analysis showed homozygosity for a unique missense change (c.130T>C, p.Cys44Arg) in TNFRSF11B that would compromise the cysteine-rich domain of OPG that binds receptor activator of NF-κB ligand (RANKL). Both parents were heterozygous for this mutation. The patient’s serum OPG level was extremely low and RANKL level markedly elevated. She responded well to rapid oral vitamin D repletion followed by pamidronate treatment given intravenously. Our patient is the first Iranian reported with JPD. Her novel mutation in TNFRSF11B plus vitamin D deficiency in infancy was associated with severe JPD uniquely complicated by craniosynostosis. Pamidronate treatment with vitamin D sufficiency can be effective treatment for the skeletal disease caused by the OPG deficiency form of JPD.
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影响因子：
5.1
作者：
REILLY, BJ;LEEMING, JM;FRASER, D
通讯作者：
FRASER, D
DOI：
10.1046/j.1432-1327.1998.2540685.x
发表时间：
1998-06-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Morinaga, T;Nakagawa, N;Higashio, K
通讯作者：
Higashio, K
影响因子：
64.5
作者：
BANNER, DW;DARCY, A;LESSLAUER, W
通讯作者：
LESSLAUER, W
影响因子：
6.2
作者：
Chong, B;Hegde, M;Cundy, T
通讯作者：
Cundy, T
DOI：
10.1016/b978-0-12-387829-8.00020-2
发表时间：
2013-01-01
期刊：
GENETICS OF BONE BIOLOGY AND SKELETAL DISEASE
影响因子：
--
作者：
Whyte, Michael P.
通讯作者：
Whyte, Michael P.