Abstract
Purpose of review:
We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease.
Recent findings:
Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.
Keywords:
ABCC6; Arterial calcification; ENPP1; GACI; PXE; Phosphate; Pyrophosphate.
Publication types
-
Review
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Abnormalities, Multiple / drug therapy
-
Abnormalities, Multiple / genetics
-
Abnormalities, Multiple / metabolism
-
Aortic Diseases / drug therapy
-
Aortic Diseases / genetics
-
Aortic Diseases / metabolism
-
Basal Ganglia Diseases / drug therapy
-
Basal Ganglia Diseases / genetics
-
Basal Ganglia Diseases / metabolism
-
Calcinosis / drug therapy
-
Calcinosis / genetics
-
Calcinosis / metabolism
-
Cartilage Diseases / drug therapy
-
Cartilage Diseases / genetics
-
Cartilage Diseases / metabolism
-
Dental Enamel Hypoplasia / drug therapy
-
Dental Enamel Hypoplasia / genetics
-
Dental Enamel Hypoplasia / metabolism
-
Diphosphates / metabolism
-
Enzyme Replacement Therapy
-
Gaucher Disease / drug therapy
-
Gaucher Disease / genetics
-
Gaucher Disease / metabolism
-
Hand Deformities, Congenital / drug therapy
-
Hand Deformities, Congenital / genetics
-
Hand Deformities, Congenital / metabolism
-
Humans
-
Hyperostosis, Cortical, Congenital / drug therapy
-
Hyperostosis, Cortical, Congenital / genetics
-
Hyperostosis, Cortical, Congenital / metabolism
-
Hyperphosphatemia / drug therapy
-
Hyperphosphatemia / genetics
-
Hyperphosphatemia / metabolism
-
Interferons / metabolism
-
Metacarpus / abnormalities
-
Metacarpus / metabolism
-
Muscular Diseases / drug therapy
-
Muscular Diseases / genetics
-
Muscular Diseases / metabolism
-
Odontodysplasia / drug therapy
-
Odontodysplasia / genetics
-
Odontodysplasia / metabolism
-
Osteoporosis / drug therapy
-
Osteoporosis / genetics
-
Osteoporosis / metabolism
-
Phosphates / metabolism
-
Progeria / drug therapy
-
Progeria / genetics
-
Progeria / metabolism
-
Pseudoxanthoma Elasticum / drug therapy
-
Pseudoxanthoma Elasticum / genetics
-
Pseudoxanthoma Elasticum / metabolism
-
Pulmonary Valve Stenosis / drug therapy
-
Pulmonary Valve Stenosis / genetics
-
Pulmonary Valve Stenosis / metabolism
-
Vascular Calcification / drug therapy
-
Vascular Calcification / genetics*
-
Vascular Calcification / metabolism
Substances
-
Diphosphates
-
Phosphates
-
Interferons
Supplementary concepts
-
Arterial calcification of infancy
-
Gaucher Disease, Type Iiic
-
Keutel syndrome
-
Singleton Merten syndrome
-
Tumoral Calcinosis, Hyperphosphatemic, Familial