Idiopathic infantile arterial calcification with cardiac, renal and central nervous system involvement

Abstract

Idiopathic infantile arterial calcification was diagnosed in a 2 week old infant with failure to thrive associated with neurological, renal and cardiac signs. Therapy with diphosphonate resulted in a complete resolution of vascular calcifications. At the age of 2 years the child is doing well but requires medical treatment for arterial hypertension.

Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy

“…(18) However, rickets or osteomalacia can develop during protracted EHDP administration for any disorder, although few reports are in the medical literature. (23,24,(38)(39)(40)(41) Amino-BPs were formulated to be more potent antiresorptive agents, and therefore less likely to interfere with mineralization at therapeutic levels. (42) Nevertheless, in 2009, treatment with an intravenous infusion of the nitrogencontaining BP, pamidronate (PMD), seemed successful for a GACI patient.…”

“…(51) Accordingly, EHDP remains a mainstay of therapy for GACI, but doses are typically tapered and then discontinued after the AC resolves. (19,24) HPP is the inborn error of metabolism caused by loss-offunction mutation(s) within the gene that encodes TNSALP. (52) PPi is a natural substrate for this cell-surface enzyme, (53) and consequently PPi accumulates extracellularly in HPP and leads to rickets or osteomalacia.…”

“…However, hypophosphatemic rickets has occurred in a few surviving GACI patients at varying ages both with and without bisphosphonate treatment. (18,19,24,25) We report a 7-year-old boy with GACI and severe skeletal toxicity from protracted EHDP therapy including rickets that mimicked severe hypophosphatasia (HPP) and bone modeling abnormalities found in osteopetrosis (OPT).…”

PC-1 Nucleoside Triphosphate Pyrophosphohydrolase Deficiency in Idiopathic Infantile Arterial Calcification

“…1 In the human condition termed idiopathic infantile arterial calcification (IIAC), calcification (hydroxyapatite deposition) in the media of large muscular arteries is associated with a stenosing, fibroproliferative medial smooth muscle cell (SMC)-mediated process, maximal in the area of the internal elastic lamina. [5][6][7][8][9] In the more than 160 cases of IIAC that have been reported, the disease most often appeared by early infancy, and was often lethal by 6 months of age, generally because of ischemic cardiomyopathy, and other complications of obstructive arteriopathy including renal artery stenosis. [5][6][7][8] In more than a dozen reported cases of IIAC, peri-articular calcifications of large joints also developed in infancy.…”

“…[5][6][7][8][9] In the more than 160 cases of IIAC that have been reported, the disease most often appeared by early infancy, and was often lethal by 6 months of age, generally because of ischemic cardiomyopathy, and other complications of obstructive arteriopathy including renal artery stenosis. [5][6][7][8] In more than a dozen reported cases of IIAC, peri-articular calcifications of large joints also developed in infancy. [5][6][7][8] One theory for the basis of pathological arterial ECM calcification has proposed an active mineralization process mediated by factors including de novo generation by cells within the arterial wall of oxidized lipids, promin-eralizing matrix vesicles, and ectopically expressed osteoblastic noncollagenous proteins such as osteopontin.…”