PDF(Pubmed)
Abstract：
BACKGROUND: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) and Hyperphosphatemic Hyperostosis Syndrome (HHS) are associated with autosomal recessive mutations in three different genes, FGF23, GALNT3 and KL, leading to reduced levels of fibroblast growth factor 23 (FGF23) and subsequent clinical effects.
RESULTS: We describe a consanguineous family with two affected siblings with HFTC and HHS caused by a novel homozygous G-to T substitution in exon 3 of GALNT3 (c.767 G > T; p.Gly256Val), demonstrating great phenotypic variation and long asymptomatic intervals. Calcific tumors appeared at 14 years of age in the male, and the female displayed episodic diaphysitis from age 9 years. Symptoms of eye involvement were present in both from childhood, and progressed into band keratopathy in the female. Abnormal dental roots and tooth loss, as well as myalgia were present in both from their mid-twenties, while the female also had calcifications in the placenta, the iliac vessels and thyroid cartilage. New calcific tumors appeared more than 20 years after the initial episodes, delaying diagnosis and treatment until the ages of 37 and 50 years, respectively. Both siblings had elevated serum phosphate levels, inappropriately elevated tubular maximum phosphate reabsorption per unit glomerular filtration rate (TmP/GFR), reduced levels of intact FGF23 and increased levels of c-terminal FGF23. Review of all 54 previously published cases of GALNT3, FGF23, and KL associated HFTC and HHS demonstrated that more subjects than previously recognized have a combined phenotype.
CONCLUSIONS: We have described HFTC and HHS in a consanguineous Caucasian family with a novel GALNT3 mutation, demonstrating new phenotypic features and significant variability in the natural course of the disease. A review of the literature, show that more subjects than previously recognized have a combined phenotype of HFTC and HHS. HHS and HFTC are two distinct phenotypes in a spectrum of GALNT3 mutation related calcification disorders, where the additional factors determining the phenotypic expression, are yet to be clarified.
RESULTS: We describe a consanguineous family with two affected siblings with HFTC and HHS caused by a novel homozygous G-to T substitution in exon 3 of GALNT3 (c.767 G > T; p.Gly256Val), demonstrating great phenotypic variation and long asymptomatic intervals. Calcific tumors appeared at 14 years of age in the male, and the female displayed episodic diaphysitis from age 9 years. Symptoms of eye involvement were present in both from childhood, and progressed into band keratopathy in the female. Abnormal dental roots and tooth loss, as well as myalgia were present in both from their mid-twenties, while the female also had calcifications in the placenta, the iliac vessels and thyroid cartilage. New calcific tumors appeared more than 20 years after the initial episodes, delaying diagnosis and treatment until the ages of 37 and 50 years, respectively. Both siblings had elevated serum phosphate levels, inappropriately elevated tubular maximum phosphate reabsorption per unit glomerular filtration rate (TmP/GFR), reduced levels of intact FGF23 and increased levels of c-terminal FGF23. Review of all 54 previously published cases of GALNT3, FGF23, and KL associated HFTC and HHS demonstrated that more subjects than previously recognized have a combined phenotype.
CONCLUSIONS: We have described HFTC and HHS in a consanguineous Caucasian family with a novel GALNT3 mutation, demonstrating new phenotypic features and significant variability in the natural course of the disease. A review of the literature, show that more subjects than previously recognized have a combined phenotype of HFTC and HHS. HHS and HFTC are two distinct phenotypes in a spectrum of GALNT3 mutation related calcification disorders, where the additional factors determining the phenotypic expression, are yet to be clarified.
摘要：
背景：高磷血症家族性肿瘤钙质沉着症（HFTC）和高磷血症增生综合征（HHS）与三种不同基因的常染色体隐性突变有关，FGF23,GALNT3和KL,导致成纤维细胞生长因子23（FGF23）水平降低和随后的临床效果。
结果：我们描述了一个近亲家庭，其中两个受影响的兄弟姐妹患有HFTC和HHS，这是由于GALNT3外显子3中的新型纯合G到T置换引起的（c.767G>T;p.Gly256Val），表现出巨大的表型变异和长的无症状间隔。钙化性肿瘤出现在14岁的男性，女性从9岁开始表现出偶发性口炎。眼睛受累的症状都存在于儿童时期，并进展为女性的带状角膜病变。牙根异常和牙齿脱落，以及从二十多岁开始出现肌痛，而女性的胎盘也有钙化，髂血管和甲状软骨.新的钙化肿瘤在最初的发作后20多年出现，将诊断和治疗推迟到37岁和50岁，分别。两个兄弟姐妹的血清磷酸盐水平都升高了，每单位肾小球滤过率（TmP/GFR）的肾小管最大磷酸盐重吸收不适当升高，完整FGF23水平降低，c末端FGF23水平升高。对先前发表的所有54例GALNT3，FGF23和KL相关的HFTC和HHS病例的审查表明，与先前公认的相比，更多的受试者具有组合表型。
结论：我们已经描述了HFTC和HHS在一个具有新型GALNT3突变的近亲高加索家族中，在疾病的自然过程中证明了新的表型特征和显着的变异性。文献综述,显示比先前识别的更多的受试者具有HFTC和HHS的组合表型。HHS和HFTC是GALNT3突变相关钙化障碍的两个不同的表型，其中决定表型表达的其他因素，还有待澄清。
结果：我们描述了一个近亲家庭，其中两个受影响的兄弟姐妹患有HFTC和HHS，这是由于GALNT3外显子3中的新型纯合G到T置换引起的（c.767G>T;p.Gly256Val），表现出巨大的表型变异和长的无症状间隔。钙化性肿瘤出现在14岁的男性，女性从9岁开始表现出偶发性口炎。眼睛受累的症状都存在于儿童时期，并进展为女性的带状角膜病变。牙根异常和牙齿脱落，以及从二十多岁开始出现肌痛，而女性的胎盘也有钙化，髂血管和甲状软骨.新的钙化肿瘤在最初的发作后20多年出现，将诊断和治疗推迟到37岁和50岁，分别。两个兄弟姐妹的血清磷酸盐水平都升高了，每单位肾小球滤过率（TmP/GFR）的肾小管最大磷酸盐重吸收不适当升高，完整FGF23水平降低，c末端FGF23水平升高。对先前发表的所有54例GALNT3，FGF23和KL相关的HFTC和HHS病例的审查表明，与先前公认的相比，更多的受试者具有组合表型。
结论：我们已经描述了HFTC和HHS在一个具有新型GALNT3突变的近亲高加索家族中，在疾病的自然过程中证明了新的表型特征和显着的变异性。文献综述,显示比先前识别的更多的受试者具有HFTC和HHS的组合表型。HHS和HFTC是GALNT3突变相关钙化障碍的两个不同的表型，其中决定表型表达的其他因素，还有待澄清。
