Idiopathic infantile arterial calcification: A surviving patient with renal artery stenosis

Abstract

Idiopathic infantile arterial calcification (IIAC) is a rare hereditary, fatal disease. Death occurs usually within the first 28 months of life. IIAC is characterized by calcifications along the internal elastic membrane and proliferation of the intimal layer of muscular arteries. Specific therapy consists of administration of diphosphonates, but its effectiveness has been a matter of controversy. We report a case treated with diphosphonates which has had an unusual outcome.

Generalized arterial calcification of infancy: two siblings with prolonged survival

“…The disease is inherited in an autosomal recessive manner so that it is not uncommon for siblings to be affected [3,13,14]. In the past, GACI was also referred to as "Idiopathic Infantile Arterial Calcification (IIAC)" [11,16]. Recently, mutations in ENPP1 encoding ecto-nucleotide pyrophosphatase/ phosphodiesterase 1 (E-NPP1) have been identified as the underlying genetic defect in most of the cases studied [10].…”

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.…”

“…(16,19) Recurrence of AC has not been reported, (20,21) but its long-term sequelae can include persistent arterial luminal narrowing from fibrosis. (19,22,23) Generalized skeletal disease has not been reported in early GACI. However, hypophosphatemic rickets has occurred in a few surviving GACI patients at varying ages both with and without bisphosphonate treatment.…”

Generalized arterial calcification of infancy: Phenotypic spectrum among three siblings including one case without obvious arterial calcifications

“…There are reports in the literature of long-term survival with resolution of calcification associated with bisphosphonate treatment [Meradji et al, 1978;Van Dyck et al, 1989;Rutsch et al, 2000] but there are also reports of spontaneous resolution of calcification [Marrott et al, 1984;Ciana et al, 2006;van der Sluis et al, 2006] and of fatal outcome despite treatment [Stuart et al, 1990]. Arterial stenosis due to intimal proliferation may also occur in areas devoid of calcification [Witzleben, 1970;Thomas et al, 1990] and persist despite resolution of calcification indicating it may be independent of calcification [Thiaville et al, 1994;Rutsch et al, 2000]. The utility of bisphosphonates for treatment of this condition therefore remains undetermined and they may not alleviate the stenosis.…”

“…The gene product, ecto-nucleotide pyrophosphatase/ phosphodiesterase 1, is a generator of extracellular inorganic pyrophosphate (PP i ), which is an inhibitor of hydroxyapatite crystal formation. Deficiency of this enzyme therefore results in deficiency of inorganic pyrophosphate [Rutsch et al, 2001] and deposition of calcium hydroxyapatite crystals between the intima and media of muscular arteries [Thiaville et al, 1994]. Calcification is usual.…”