title: PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.
abstract: Inogranic pyrophosphate (PPi) inhibits hydroxyapatite deposition, and mice deficient in the PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) Plasma cell membrane glycoprotein-1 (PC-1) develop peri-articular and arterial calcification in early life. In idiopathic infantile arterial calcification (IIAC), hydroxyapatite deposition and smooth muscle cell (SMC) proliferation occur, sometimes associated with peri-articular calcification. Thus, we assessed PC-1 expression and PPi metabolism in a 25-month-old boy with IIAC and peri-articular calcifications. Plasma PC-1 was <1 ng/ml by enzyme-linked immunosorbent assay in the proband, but 10 to 30 ng/ml in unaffected family members and controls. PC-1 functioned to raise extracellular PPi in cultured aortic SMCs. However, PC-1 was sparse in temporal artery lesion SMCs in the proband, unlike the case for SMCs in atherosclerotic carotid artery lesions of unrelated adults. Proband plasma and explant-cultured dermal fibroblast NTPPPH and PPi were markedly decreased. The proband was heterozygous at the PC-1 locus, and sizes of PC-1 mRNA and polypeptide, and the PC-1 mRNA-coding region sequence were normal in proband fibroblasts. However, immunoreactive PC-1 protein was relatively sparse in proband fibroblasts. In conclusion, deficient extracellular PPi and a deficiency of PC-1 NTPPPH activity can be associated with human infantile arterial and peri-articular calcification, and may help explain the sharing of certain phenotypic features between some IIAC patients and PC-1-deficient mice.
authors.affiliation: Department of Pediatrics, Municipal Children's Hospital, Dortmund, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Rutsch
authors.forename: S
authors.initials: S
authors.lastname: Vaingankar
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: I
authors.initials: I
authors.lastname: Goldfine
authors.forename: B
authors.initials: B
authors.lastname: Maddux
authors.forename: P
authors.initials: P
authors.lastname: Schauerte
authors.forename: H
authors.initials: H
authors.lastname: Kalhoff
authors.forename: K
authors.initials: K
authors.lastname: Sano
authors.forename: W A
authors.initials: WA
authors.lastname: Boisvert
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: R
authors.initials: R
authors.lastname: Terkeltaub
mesh_terms: D001161:Arteriosclerosis / Q000201:enzymology* / Q000473:pathology; D015152:Blotting, Northern; D002114:Calcinosis / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D011756:Diphosphates / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D010375:Pedigree; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012867:Skin / Q000166:cytology / Q000378:metabolism
chemical_list: D011756:Diphosphates; D008562:Membrane Glycoproteins; D012313:RNA; D004247:DNA; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; C021895:nucleoside triphosphate pyrophosphatase