Arterial calcification of infancy

A severe hereditary autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and STENOSIS due to myointimal proliferation. It is often fatal within the first 6 months of life because of MYOCARDIAL ISCHEMIA resulting in refractory HEART FAILURE. Mutations in the ENPP1 gene have been identified. OMIM: 208000

Also Known As:

Networked: 92 relevant articles (8 outcomes, 8 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hypertension (High Blood Pressure)
2.	Vascular Calcification
3.	Hyperplasia
4.	Rickets (Rachitis)
5.	Heart Failure

Experts

1.	Rutsch, Frank: 17 articles (01/2022 - 01/2005)
2.	Li, Qiaoli: 12 articles (01/2022 - 07/2013)
3.	Nitschke, Yvonne: 12 articles (01/2022 - 12/2008)
4.	Uitto, Jouni: 12 articles (01/2022 - 07/2013)
5.	Váradi, András: 7 articles (01/2022 - 01/2013)
6.	Levine, Michael A: 6 articles (01/2022 - 01/2015)
7.	Pomozi, Viola: 6 articles (01/2022 - 01/2013)
8.	Le Saux, Olivier: 5 articles (04/2021 - 01/2013)
9.	Sundberg, John P: 5 articles (01/2019 - 01/2015)
10.	Braddock, Demetrios T: 4 articles (01/2022 - 12/2015)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Arterial calcification of infancy:

1.	Diphosphonates (Bisphosphonates)IBA 01/01/2016 - "We previously characterized the Enpp1(asj) mutant mouse as a model of generalized arterial calcification of infancy, and we have now explored the potential efficacy of bisphosphonates, nonhydrolyzable PPi analogs, in preventing ectopic mineralization in these mice. " 11/01/2018 - "Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. " 06/01/2020 - "However, there is a paucity of data on the antenatal use of bisphosphonates for GACI. " 06/01/2020 - "Bisphosphonates have been used with some success in the treatment of GACI. " 01/01/2019 - "Treatment with bisphosphonates has been proposed as a means of reducing arterial calcifications in GACI patients, although there is no formalized treatment approach. "
2.	Proteins (Proteins, Gene)FDA Link 10/08/2018 - "In this study, the efficacy of a recombinant human ENPP1 protein therapeutic (rhENPP1) was tested in Enpp1asj-2J homozygous mice (Asj-2J or Asj-2J hom), a model previously described to show extensive mineralization in the arterial vasculature, similar to GACI patients. " 11/15/2022 - "Truncated GacI proteins having only the GT or the PP domain showed comparable catalytic activity with the full-length GacI, indicating that domain separation does not significantly affect their respective catalytic activity. " 10/29/2018 - "Furthermore, we aimed to effectively prevent and treat neointima formation in an animal model of GACI through the systemic administration of recombinant human (rh)ENPP1-Fc protein. " 10/29/2018 - "Furthermore, subcutaneous rhENPP1-Fc protein replacement was effective in preventing and treating intimal hyperplasia induced by carotid ligation in an animal model of GACI. " 12/01/2015 - "Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. "
3.	Phosphates (Orthophosphate)IBA 12/01/2008 - "A phosphate-poor diet markedly increases survival of NPP1 null mice, a model of generalized arterial calcification of infancy. " 05/01/2016 - "Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification." 05/01/2016 - "Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. " 01/01/2022 - "Biallelic ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency induces vascular/soft tissue calcifications in generalized arterial calcification of infancy (GACI), and low bone mass with phosphate-wasting rickets in GACI survivors (autosomal hypophosphatemic rickets type-2). " 01/01/2017 - "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. "
4.	MineralsIBA 07/01/2013 - "This overview will highlight diseases with mineral deposition in the skin and vascular connective tissues, as exemplified by familial tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, and arterial calcification due to CD73 deficiency. " 01/01/2015 - "We found that ETD, but not AST, at the 12x dosage, significantly reduced mineralization, suggesting that selected bisphosphonates may be helpful for prevention of mineral deposits in PXE and GACI caused by mutations in the ABCC6 gene, when combined with careful monitoring of efficacy and potential side-effects. " 01/01/2020 - "The man alone also carried novel heterozygous missense variants within two additional genes that condition mineral homeostasis and are the basis for autosomal recessive disorders: CYP27B1 underlying vitamin D dependent rickets, type 1, and ABCC6 underlying both generalized arterial calcification of infancy, type 2 and pseudoxanthoma elasticum (PXE). "
5.	Phenobarbital (Luminal)FDA Link 05/01/1990 - "We describe a patient with idiopathic arterial calcification of infancy and the following unusual features of the disease: (1) prolonged survival until age 11 years, (2) discordance between the extent of vascular calcification and clinical manifestations of arterial luminal occlusion, (3) a large area of myocardial calcification, (4) symptoms of cerebral-vascular insufficiency, and (5) spontaneous resolution of hypertension." 11/01/2015 - "Idiopathic arterial calcification of infancy is a rare autosomal recessive disease, characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima which causes luminal narrowing. "
6.	MagnesiumIBA 06/13/2017 - "We previously characterized the Enpp1asjmutant mouse as a model of GACI, and we have now explored the effect of elevated dietary magnesium (five-fold) in pregnant mothers and continuing for the first 14 weeks of postnatal life. " 06/13/2017 - "Elevated dietary magnesium during pregnancy and postnatal life prevents ectopic mineralization in Enpp1asj mice, a model for generalized arterial calcification of infancy." 01/01/2019 - "Magnesium and Anti-phosphate Treatment with Bisphosphonates for Generalised Arterial Calcification of Infancy: A Case Report" 01/01/2019 - "The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. "
7.	Vitamin KFDA Link 03/15/2015 - "These data suggest that vitamin K could be a beneficial treatment for human patients with PXE or GACI. " 03/15/2015 - "Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI." 03/15/2015 - "Vitamin K also reduced ectopic mineralisation in a zebrafish model of GACI, and warfarin exacerbated the mineralisation phenotype in both mutant lines. "
8.	Calcium Carbonate (Limestone)FDA Link 01/01/2019 - "The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. "
9.	Etidronic Acid (HEDP)FDA LinkGeneric 07/01/2015 - "In the present study, we used the Enpp1-/- mouse model of GACI to examine the effects of etidronate treatment (100 µg/kg), on vascular and skeletal calcification. " 06/01/2020 - "Skeletal abnormalities secondary to antenatal etidronate treatment for suspected generalised arterial calcification of infancy." 10/29/2018 - "In contrast, neither PPi nor etidronate, a current off-label treatment for GACI, had an effect on VSMC proliferation. " 07/20/2018 - "The results suggest that etidronate may offer a potential treatment modality for PXE and GACI caused by ABCC6 mutations. " 07/01/2015 - "Effects of etidronate on the Enpp1⁻/⁻ mouse model of generalized arterial calcification of infancy."
10.	N- (4'- fluorobutyrophenone)- 4- (4- chlorophenyl)pyridinium (HPP(+))IBA 10/01/2020 - "In this perspective, we compare and contrast dental defects in primary teeth associated with XLH, HPP, and GACI, briefly reviewing genetic and biochemical features of these disorders and findings of clinical and preclinical studies to date, including some of our own recent observations. " 01/01/2019 - "In direct contrast to HPP, deficiency of ePPi characterizes the inborn-errors-of-metabolism generalized arterial calcification of infancy (GACI) and pseudoxanthoma elasticum (PXE). " 06/01/2020 - "In this paper, we report development of the skeletal changes suggestive of hypophosphatasia (HPP) in an infant with GACI, whose mother was treated with etidronate during pregnancy. " 06/01/2020 - "We believe, this is the first report of skeletal changes suggestive of HPP, arising secondary to antenatal etidronate (first generation bisphosphonate) used for the treatment of suspected GACI due to a heterozygous ABCC6 mutation."

Therapies and Procedures

1.	Therapeutics 05/01/2020 - "The positive results led to the conclusion that the produced nanoparticles might be a promising therapy in the treatment of GACI and PXE." 04/27/2021 - "At present, therapies only exist to alleviate symptoms for both PXE and GACI; however, extensive studies have resulted in several novel approaches to treating PXE and GACI. " 07/16/2013 - "A diagnosis of Idiopathic infantile arterial calcification was made and a trial of Editronate therapy was given without success. " 01/01/2018 - "Here we present a case report of GACI in a male infant with a new familial mutation of the ENPP1 gene and the clinical outcome after biphosphonates therapy. " 09/01/2014 - "Our results indicate that systemic PPi is relatively stable and that PXE, generalized arterial calcification of infancy, and other ectopic mineralization disorders could be treated with PPi supplementation therapy."
2.	Ligation 10/29/2018 - "Furthermore, subcutaneous rhENPP1-Fc protein replacement was effective in preventing and treating intimal hyperplasia induced by carotid ligation in an animal model of GACI. "
3.	Enzyme Replacement Therapy 10/08/2018 - "ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy." 10/08/2018 - "This study suggests that ENPP1 enzyme replacement therapy could be a more effective GACI therapeutic than bisphosphonates, treating not just the vascular calcification, but also the hypertension that eventually leads to cardiac failure in GACI patients."
4.	Withholding Treatment 02/01/2013 - "With EHDP therapy for GACI, AC may resolve without recurrence upon treatment cessation. "
5.	Renal Replacement Therapy (Therapies, Renal Replacement) 10/01/2023 - "She was clinically diagnosed with GACI and initiated on supportive care including renal replacement therapy. "