From variome to phenome:Pathogenesis,diagnosis and management of ectopic mineralization disorders  

作　　者：Eva YG De Vilder Olivier M Vanakker 

机构地区：[1]Center for Medical Genetics,Ghent University Hospital [2]Department of Ophthalmology,Ghent University Hospital

出　　处：《World Journal of Clinical Cases》2015年第7期556-574,共19页世界临床病例杂志

基　　金：Supported by The Research Foundation Flanders(FWO)(FWO14/ASP/084),Vanakker OM is a senior clinical investigator at the Fund for Scientific Research-Flanders;Contract grant sponsor:FWO grant No G.0241.11N;Methusalem grant No.08/01M01108

摘　　要：Ectopic mineralization- inappropriate biomineralization in soft tissues- is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge(variome) to the phenotype(phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73(NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification.Ectopic mineralization- inappropriate biomineralization in soft tissues- is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge(variome) to the phenotype(phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73(NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification.

关 键 词：Ectopic mineralization Pseudoxanthoma elasticum Pseudoxanthoma elasticum-like SYNDROME Generalized ARTERIAL CALCIFICATION of INFANCY Keutel SYNDROME Idiopathic basal GANGLIA CALCIFICATION ARTERIAL CALCIFICATION due to CD73 deficiency Hyperphosphatemic familial tumoral CALCINOSIS Etiology Phenotype 

分 类 号：R596[医药卫生—内科学]