GACI
MCID: ART035
MIFTS: 58

Arterial Calcification of Infancy (GACI)

Categories: Cardiovascular diseases, Rare diseases

Aliases & Classifications for Arterial Calcification of Infancy

MalaCards integrated aliases for Arterial Calcification of Infancy:

Name: Arterial Calcification of Infancy 12 73 20 44 15 70
Generalized Arterial Calcification of Infancy 12 25 43 58 36 29
Idiopathic Infantile Arterial Calcification 12 25 20 43 58
Occlusive Infantile Arteriopathy 20 43 58
Iiac 25 20 43
Idiopathic Obliterative Arteriopathy 43 58
Infantile Arteriosclerosis 12 58
Gaci 25 43
Diffuse Arterial Calcifying Elastopathy of Infancy 43
Generalized Arterial Calcification in Infancy 20
Coronary Sclerosis, Medial, of Infancy 6
Medial Coronary Sclerosis of Infancy 43
Arteriopathia Calcificans Infantum 43
Infantile Calcifying Arteriopathy 43

Characteristics:

Orphanet epidemiological data:

58
generalized arterial calcification of infancy
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 58  
Rare circulatory system diseases


Summaries for Arterial Calcification of Infancy

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 51608 Definition A rare genetic vascular disease characterized by early onset (between in utero to infancy) of extensive calcification and stenosis of the large and medium sized arteries. Presentation is typically with respiratory distress, congestive heart failure and systemic hypertension. Epidemiology Approximately 300 cases have been reported worldwide in the medical literature. The prevalence is unknown; however, based on carrier frequency of the recognized pathogenic variants, the frequency of 1/566,000 has been suggested. Clinical description Disease onset is either early (in utero to within the first week of life) or late (median age three months). Early-onset disease presents variably with fetal distress, heart failure, polyhydramnios, hypertension, respiratory distress, hydrops fetalis, edema, visceral effusions, cyanosis, cardiomegaly, and ascites. Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension, and edema. Additional findings can include extravascular calcifications (particularly periarticular), typical skin and retinal manifestations of pseudoxanthoma elasticum, hearing loss, and development of rickets after infancy. Pathologically, the condition is characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima, which causes luminal narrowing. Etiology Causal mutations have been identified in the genes ENPP1 ( chromosome 6q23.2) and ABCC6 (chromosome 16p13.11) respectively encoding ectonucleotide pyrophosphatase/ phosphodiesterase 1 and multidrug resistance-associated protein 6, a transmembrane protein belonging to the family of ATP-binding cassette (ABC) transport proteins. Pathological variants lead to aberrant tissue mineralization, and the subsequent luminal narrowing invariably leads to coronary arterial occlusion and myocardial ischemia or stenoses of different arteries leading to end- organ damage. ENPP1 mutations also cause autosomal recessive hypophosphatemic rickets, which is associated with longer survival. Diagnostic methods Diagnosis of is made by the combination of clinical, imaging or histopathological findings, together with genetic results. The preferred imaging modality to assess calcifications extension is whole-body computed tomography combined with CT angiography. Differential diagnosis Differential diagnosis includes endocardial fibroelastosis, myocardititis, storage disorders, infarction, anomalous insertion of the coronary arteries, cardiac anomalies, metastatic calcification due to renal disease, hypervitaminosis D, infections, and non-immune fetal hydrops, Takayasu arteriitis. Antenatal diagnosis Antenatal diagnosis has been reported, with findings of arterial calcifications, hydrops, abnormal cardiac contractility, and hyperechoic kidneys. The diagnosis is essential for genetic counseling, and for screening of siblings at risk for developing the disease. Genetic counseling The pattern of inheritance is autosomal recessive. The sibling-recurrence risk is 25%. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family are known. Management and treatment Use of bisphosphonates appears to significantly increase survival. Standard anti-hypertensive therapy is warranted for hypertension. Aspirin therapy is warranted in those with severe coronary stenosis who are at increased risk for coronary thrombosis. Anti-hypertensive therapy is warranted for hypertension. Treatment of hypophosphatemic rickets involves calcitriol and oral phosphate supplements. It seems prudent to avoid the use of warfarin if possible. Where endotracheal intubation is required, lateral cervical spine x-ray is recommended to evaluate for cervical spine fusion, and thereby avoid secondary complications. Prognosis Prognosis is poor; most infants die from myocardial infarction within the first year of life, with the greatest number of deaths occurring within the first six months. Nevertheless, long-term survival into the second and third decade has been reported.

MalaCards based summary : Arterial Calcification of Infancy, also known as generalized arterial calcification of infancy, is related to pseudoxanthoma elasticum and calcification of joints and arteries. An important gene associated with Arterial Calcification of Infancy is ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1), and among its related pathways/superpathways are Purine metabolism and Starch and sucrose metabolism. Affiliated tissues include heart, eye and bone, and related phenotypes are calcification of the aorta and hepatic calcification

Disease Ontology : 12 A vascular disease that is characterized by generalized calcification of the arterial internal elastic lamina, leading to rupture of the lamina and occlusive changes in the tunica intima with stenosis and decreased elasticity of the vessel wall.

MedlinePlus Genetics : 43 Generalized arterial calcification of infancy (GACI) is a disorder affecting the circulatory system that becomes apparent before birth or within the first few months of life. It is characterized by abnormal accumulation of the mineral calcium (calcification) in the walls of the blood vessels that carry blood from the heart to the rest of the body (the arteries). This calcification often occurs along with thickening of the lining of the arterial walls (the intima). These changes lead to narrowing (stenosis) and stiffness of the arteries, which forces the heart to work harder to pump blood. As a result, heart failure may develop in affected individuals, with signs and symptoms including difficulty breathing, accumulation of fluid (edema) in the extremities, a bluish appearance of the skin or lips (cyanosis), severe high blood pressure (hypertension), and an enlarged heart (cardiomegaly).People with GACI may also have calcification in other organs and tissues, particularly around the joints. In addition, they may have hearing loss or softening and weakening of the bones (rickets).Some individuals with GACI also develop features similar to those of another disorder called pseudoxanthoma elasticum (PXE). PXE is characterized by the accumulation of calcium and other minerals (mineralization) in elastic fibers, which are a component of connective tissue. Connective tissue provides strength and flexibility to structures throughout the body. Features characteristic of PXE that also occur in GACI include yellowish bumps called papules on the underarms and other areas of skin that touch when a joint bends (flexor areas); and abnormalities called angioid streaks affecting tissue at the back of the eye, which can be detected during an eye examination.As a result of the cardiovascular problems associated with GACI, individuals with this condition often do not survive past infancy, with death typically caused by a heart attack or stroke. However, affected individuals who survive their first six months, known as the critical period, can live into adolescence or early adulthood.

KEGG : 36 Generalized arterial calcification of infancy (GACI) is a rare and often fatal genetic disorder, characterized by calcification of the internal elastic lamina, fibrotic myointimal proliferation of muscular arteries, and resultant arterial stenosis. GACI is associated with biallelic inactivating mutations in ENPP1 in about 75% of the cases. ENPP1 generates PPi that inhibits hydroxyapatite crystal growth.

Wikipedia : 73 Generalized arterial calcification of infancy (GACI) is an extremely rare genetic disorder. It is caused... more...

GeneReviews: NBK253403

Related Diseases for Arterial Calcification of Infancy

Diseases related to Arterial Calcification of Infancy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 124)
# Related Disease Score Top Affiliating Genes
1 pseudoxanthoma elasticum 31.3 SPP1 MGP GGCX ENPP1 ANKH ALPL
2 calcification of joints and arteries 31.2 NT5E MGP GGCX ENPP1 ARSJ ANKH
3 brittle bone disorder 30.6 SPP1 PHEX NT5E ALPL
4 hypophosphatemic rickets, x-linked recessive 30.5 SLC34A3 PHEX FGF23 ENPP1
5 hypercementosis 30.2 PHOSPHO1 ENPP1
6 calciphylaxis 30.1 NT5E MGP FGF23 AHSG
7 rickets 30.1 SLC34A3 PHEX KL FGF23 ENPP1 ALPL
8 hypervitaminosis d 29.9 KL GALNT3 FGF23
9 nephrocalcinosis 29.9 SPP1 SLC34A3 PHEX
10 arteriosclerosis 29.9 SPP1 MGP KL ACE
11 ankylosis 29.8 SLC20A2 PHOSPHO1 ENPP1 ANKH
12 hypophosphatasia 29.6 SPP1 PHOSPHO1 PHEX FGF23 ENPP1 ANKH
13 angioid streaks 29.6 MGP GGCX GALNT3 ENPP1 AHSG ABCC6
14 hypophosphatemia 28.8 SPP1 SLC34A3 PHEX KL FGF23 FAM20C
15 calcinosis 28.8 SPP1 PHEX MGP KL GALNT3 FGF23
16 autosomal recessive hypophosphatemic rickets 28.6 SLC34A3 PHEX KL GALNT3 FGF23 FAM20C
17 hypophosphatemic rickets, x-linked dominant 27.9 SPP1 SLC34A3 PHEX KL GALNT3 FGF23
18 arterial calcification, generalized, of infancy, 1 11.8
19 arterial calcification, generalized, of infancy, 2 11.8
20 autosomal recessive disease 10.6
21 oncogenic osteomalacia 10.3 PHEX FGF23
22 opsismodysplasia 10.3 PHEX FGF23
23 acute apical periodontitis 10.3 PHEX ACE
24 tumoral calcinosis, normophosphatemic, familial 10.3 ENPP1 ABCC6
25 glossopharyngeal nerve disease 10.2 SLC20A2 ACE
26 chlorhexidine allergy 10.2 ENPP3 ACE
27 congestive heart failure 10.2
28 patella, chondromalacia of 10.2 NT5E ACE
29 hypophosphatasia, infantile 10.2 PHOSPHO1 ENPP1 ALPL
30 chondrocalcinosis 10.2 ENPP1 ANKH ALPL
31 hydrops fetalis, nonimmune 10.1
32 lymphatic malformation 7 10.1
33 respiratory failure 10.1
34 hemopericardium 10.1
35 pericardial effusion 10.1
36 hyperparathyroidism 10.1 PHEX KL FGF23
37 calcific tendinitis 10.1 SPP1 PHOSPHO1
38 bursitis 10.1 PHOSPHO1 ALPL
39 secondary hyperparathyroidism 10.1 PHEX KL FGF23
40 blount's disease 10.1 SLC34A3 FGF23
41 inflammatory bowel disease 14 10.1 SPP1 NT5E
42 vitamin k deficiency bleeding 10.1 MGP GGCX
43 hepatocellular clear cell carcinoma 10.1 KL FGF23
44 fanconi renotubular syndrome 2 10.1 SLC34A3 PHEX
45 atrial standstill 1 10.0
46 cardiac arrest 10.0
47 pulmonary edema 10.0
48 gastroenteritis 10.0
49 aortic aneurysm 10.0
50 chronic intestinal vascular insufficiency 10.0

Graphical network of the top 20 diseases related to Arterial Calcification of Infancy:



Diseases related to Arterial Calcification of Infancy

Symptoms & Phenotypes for Arterial Calcification of Infancy

Human phenotypes related to Arterial Calcification of Infancy:

58 31 (show top 50) (show all 65)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 calcification of the aorta 58 31 hallmark (90%) Very frequent (99-80%) HP:0004963
2 hepatic calcification 58 31 hallmark (90%) Very frequent (99-80%) HP:0006559
3 hypertension 58 31 frequent (33%) Frequent (79-30%) HP:0000822
4 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
5 osteomalacia 58 31 frequent (33%) Frequent (79-30%) HP:0002749
6 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
7 fetal distress 58 31 frequent (33%) Frequent (79-30%) HP:0025116
8 coronary artery calcification 58 31 frequent (33%) Frequent (79-30%) HP:0001717
9 respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0002098
10 cyanosis 58 31 frequent (33%) Frequent (79-30%) HP:0000961
11 adrenal calcification 58 31 frequent (33%) Frequent (79-30%) HP:0010512
12 medial calcification of large arteries 58 31 frequent (33%) Frequent (79-30%) HP:0004966
13 hypophosphatemic rickets 58 31 frequent (33%) Frequent (79-30%) HP:0004912
14 left ventricular systolic dysfunction 58 31 frequent (33%) Frequent (79-30%) HP:0025169
15 medullary nephrocalcinosis 58 31 frequent (33%) Frequent (79-30%) HP:0012408
16 medial calcification of medium-sized arteries 58 31 frequent (33%) Frequent (79-30%) HP:0012457
17 periarticular calcification 58 31 frequent (33%) Frequent (79-30%) HP:0025477
18 vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002013
19 fever 58 31 occasional (7.5%) Occasional (29-5%) HP:0001945
20 cardiomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001640
21 ascites 58 31 occasional (7.5%) Occasional (29-5%) HP:0001541
22 hydrops fetalis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001789
23 failure to thrive in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001531
24 irritability 58 31 occasional (7.5%) Occasional (29-5%) HP:0000737
25 arthralgia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002829
26 fused cervical vertebrae 58 31 occasional (7.5%) Occasional (29-5%) HP:0002949
27 mixed hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000410
28 pericardial effusion 58 31 occasional (7.5%) Occasional (29-5%) HP:0001698
29 abnormality of the knee 58 31 occasional (7.5%) Occasional (29-5%) HP:0002815
30 stapes ankylosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000381
31 abnormal calcification of the carpal bones 58 31 occasional (7.5%) Occasional (29-5%) HP:0009164
32 abnormal retinal artery morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0000630
33 ventricular hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001714
34 pancreatic calcification 58 31 occasional (7.5%) Occasional (29-5%) HP:0005213
35 elevated alkaline phosphatase of bone origin 58 31 occasional (7.5%) Occasional (29-5%) HP:0010639
36 abnormality of the hip joint 58 31 occasional (7.5%) Occasional (29-5%) HP:0001384
37 recurrent spontaneous abortion 58 31 occasional (7.5%) Occasional (29-5%) HP:0200067
38 stippled calcification of the shoulder 58 31 occasional (7.5%) Occasional (29-5%) HP:0003836
39 stippled calcification of the elbow 58 31 occasional (7.5%) Occasional (29-5%) HP:0003941
40 cortical nephrocalcinosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0012409
41 weak pulse 58 31 occasional (7.5%) Occasional (29-5%) HP:0032553
42 cerebral calcification 58 31 very rare (1%) Very rare (<4-1%) HP:0002514
43 aortic dissection 58 31 very rare (1%) Very rare (<4-1%) HP:0002647
44 transient ischemic attack 58 31 very rare (1%) Very rare (<4-1%) HP:0002326
45 severe global developmental delay 58 31 very rare (1%) Very rare (<4-1%) HP:0011344
46 pulmonary arterial hypertension 58 31 very rare (1%) Very rare (<4-1%) HP:0002092
47 gangrene 58 31 very rare (1%) Very rare (<4-1%) HP:0100758
48 retinal hemorrhage 58 31 very rare (1%) Very rare (<4-1%) HP:0000573
49 encephalomalacia 58 31 very rare (1%) Very rare (<4-1%) HP:0040197
50 calcification of the auricular cartilage 58 31 very rare (1%) Very rare (<4-1%) HP:0005103

GenomeRNAi Phenotypes related to Arterial Calcification of Infancy according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00240-S-1 9.62 GGCX SLC34A3
2 Decreased viability GR00249-S 9.62 ALPL ANKH ENPP1 SPP1
3 Decreased viability GR00381-A-1 9.62 FAM20C MGP NT5E SLC34A3
4 Decreased viability GR00381-A-2 9.62 MGP
5 Decreased viability GR00381-A-3 9.62 MGP
6 Decreased viability GR00386-A-1 9.62 ALPL ANKH FAM20C KL SLC20A2 SLC34A3
7 Decreased viability GR00402-S-2 9.62 ABCC6 ENPP1

MGI Mouse Phenotypes related to Arterial Calcification of Infancy:

46 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.5 ABCC6 ACE AHSG ALPL ANKH ENPP1
2 homeostasis/metabolism MP:0005376 10.43 ABCC6 ACE AHSG ALPL ANKH ENPP1
3 cardiovascular system MP:0005385 10.4 ABCC6 ACE ALPL ANKH ENPP1 FGF23
4 hematopoietic system MP:0005397 10.31 ACE ALPL ANKH ENPP3 FAM20C FGF23
5 craniofacial MP:0005382 10.29 ABCC6 ALPL ANKH ENPP1 FAM20C GALNT3
6 immune system MP:0005387 10.23 ACE ALPL ANKH ENPP1 ENPP3 FAM20C
7 mortality/aging MP:0010768 10.21 ACE ALPL ANKH ENPP1 ENPP3 FAM20C
8 digestive/alimentary MP:0005381 10.14 ALPL ENPP3 FAM20C FGF23 GALNT3 KL
9 adipose tissue MP:0005375 10.11 ACE ALPL ENPP1 GGCX KL PHEX
10 limbs/digits/tail MP:0005371 10.1 AHSG ALPL ANKH ENPP1 FAM20C FGF23
11 integument MP:0010771 10.09 ABCC6 ENPP1 FGF23 GALNT3 GGCX KL
12 hearing/vestibular/ear MP:0005377 10.05 AHSG ANKH ENPP1 FAM20C KL PHEX
13 renal/urinary system MP:0005367 10.03 ABCC6 ACE ENPP1 FAM20C FGF23 GALNT3
14 muscle MP:0005369 9.92 AHSG ALPL ANKH ENPP1 GALNT3 KL
15 reproductive system MP:0005389 9.81 ACE ALPL ANKH FAM20C FGF23 GALNT3
16 respiratory system MP:0005388 9.5 ALPL ANKH ENPP3 FGF23 KL MGP
17 skeleton MP:0005390 9.5 AHSG ALPL ANKH ENPP1 FAM20C FGF23

Drugs & Therapeutics for Arterial Calcification of Infancy

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Natural History of Generalized Arterial Calcification of Infancy (GACI) With or Without Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) or Pseudoxanthoma Elasticum (PXE) Unknown status NCT03758534
2 A Natural History Study of Patients With Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) Completed NCT03478839
3 Understanding the Spectrum of ENPP1 Deficiency and Acute ABCC6 Deficiency Through the Eyes of Patients and Parents; Burden of Illness Perspectives From Patients and Parents Who Speak English, French or German Completed NCT04372446

Search NIH Clinical Center for Arterial Calcification of Infancy

Cochrane evidence based reviews: arterial calcification of infancy

Genetic Tests for Arterial Calcification of Infancy

Genetic tests related to Arterial Calcification of Infancy:

# Genetic test Affiliating Genes
1 Generalized Arterial Calcification of Infancy 29

Anatomical Context for Arterial Calcification of Infancy

MalaCards organs/tissues related to Arterial Calcification of Infancy:

40
Heart, Eye, Bone, Skin

Publications for Arterial Calcification of Infancy

Articles related to Arterial Calcification of Infancy:

(show top 50) (show all 187)
# Title Authors PMID Year
1
Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. 25 6 61
22209248 2012
2
Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. 61 25 6
20137773 2010
3
Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. 6 25 61
20016754 2008
4
Generalized arterial calcification of infancy: two siblings with prolonged survival. 25 6 61
16315058 2006
5
Generalized arterial calcification of infancy: different clinical courses in two affected siblings. 25 6 61
15940697 2005
6
Idiopathic infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation. 6 25
16573612 2006
7
Effects of Different Variants in the ENPP1 Gene on the Functional Properties of Ectonucleotide Pyrophosphatase/Phosphodiesterase Family Member 1. 61 6
27467858 2016
8
An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. 61 6
20034067 2010
9
Generalized arterial calcification of infancy: phenotypic spectrum among three siblings including one case without obvious arterial calcifications. 6 61
19206175 2009
10
The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI). 61 6
15605415 2005
11
Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI). 61 25
33005041 2021
12
Severe early-onset manifestations of pseudoxanthoma elasticum resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB: transient improvement in ectopic calcification with sodium thiosulfate. 25 61
31646622 2020
13
Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management. 25 61
32172442 2020
14
Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations. 61 25
31826312 2020
15
Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency. 61 25
31805212 2020
16
Novel homozygous ENPP1 mutation causes generalized arterial calcifications of infancy, thrombocytopenia, and cardiovascular and central nervous system syndrome. 6
31444901 2019
17
Magnesium and Anti-phosphate Treatment with Bisphosphonates for Generalised Arterial Calcification of Infancy: A Case Report 25 61
30525344 2019
18
ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the generation of AMP. 61 25
30369595 2018
19
ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy. 61 25
30158213 2018
20
Mutation spectrum in the ABCC6 gene and genotype-phenotype correlations in a French cohort with pseudoxanthoma elasticum. 6
28102862 2017
21
Elevated dietary magnesium during pregnancy and postnatal life prevents ectopic mineralization in Enpp1asj mice, a model for generalized arterial calcification of infancy. 61 25
28402956 2017
22
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. 61 25
26624227 2015
23
Heart transplant and 2-year follow up in a child with generalized arterial calcification of infancy. 61 25
25367056 2014
24
[GACI syndrome: a case report with a neonatal beginning]. 25 61
24768072 2014
25
Hearing loss is part of the clinical picture of ENPP1 loss of function mutation. 25 61
24216977 2014
26
Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy. 61 25
22972716 2013
27
Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin. 25 61
23269929 2012
28
Generalized Arterial Calcification of Infancy: Fatal Clinical Course Associated with a Novel Mutation in ENPP1. 25 61
23430823 2011
29
Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. 6
18800149 2009
30
The difficulty in diagnosing idiopathic arterial calcification of infancy, its variation in presentation, and the importance of autopsy. 61 25
18842162 2008
31
Pseudoxanthoma elasticum: the end of the autosomal dominant segregation myth. 6
16541094 2006
32
Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. 6
16086317 2005
33
New findings in idiopathic arterial calcification of infancy detected by MDCT. 25 61
16037532 2005
34
Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. 6
12881724 2003
35
Analysis of the frequent R1141X mutation in the ABCC6 gene in pseudoxanthoma elasticum. 6
12714611 2003
36
Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa. 6
12384774 2002
37
Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. 6
12176944 2002
38
Compound heterozygosity for a recurrent 16.5-kb Alu-mediated deletion mutation and single-base-pair substitutions in the ABCC6 gene results in pseudoxanthoma elasticum. 6
11179012 2001
39
Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11. 6
11439001 2001
40
Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. 6
10811882 2000
41
Idiopathic arterial calcification of infancy: sonographic and magnetic resonance findings with pathologic correlation. 61 25
9545482 1998
42
Idiopathic arterial calcification of infancy: a case with prolonged survival. 61 25
2400650 1990
43
Generalized arterial calcification of infancy: three case reports, including spontaneous regression with long-term survival. 61 25
6747757 1984
44
Disseminated arterial calcification associated with acardius acephalus. 61 25
6684415 1983
45
Imaging studies in pediatric fibromuscular dysplasia (FMD): a single-center experience. 25
29869115 2018
46
The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. 25
28349240 2017
47
Differences between the pediatric and adult presentation of fibromuscular dysplasia: results from the US Registry. 25
26525198 2016
48
Cole Disease Results from Mutations in ENPP1. 25
24075184 2013
49
The mystery of persistent pulmonary hypertension: an idiopathic infantile arterial calcification. 25
23855924 2013
50
Warfarin accelerates ectopic mineralization in Abcc6(-/-) mice: clinical relevance to pseudoxanthoma elasticum. 25
23415960 2013

Variations for Arterial Calcification of Infancy

ClinVar genetic disease variations for Arterial Calcification of Infancy:

6 (show top 50) (show all 244)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ABCC6 GRCh37/hg19 16p13.11(chr16:16248791-16260443) copy number loss Pathogenic 870399 GRCh37: 16:16248791-16260443
GRCh38:
2 ENPP1 NM_006208.3(ENPP1):c.1072_1082del (p.Gln358fs) Deletion Pathogenic 13587 rs1554203715 GRCh37: 6:132185691-132185701
GRCh38: 6:131864551-131864561
3 ENPP1 NM_006208.3(ENPP1):c.1737G>C (p.Leu579Phe) SNV Pathogenic 13588 rs121918024 GRCh37: 6:132198145-132198145
GRCh38: 6:131877005-131877005
4 ENPP1 NM_006208.3(ENPP1):c.1025G>T (p.Gly342Val) SNV Pathogenic 13591 rs121918025 GRCh37: 6:132182844-132182844
GRCh38: 6:131861704-131861704
5 ENPP1 NM_006208.3(ENPP1):c.1112A>T (p.Tyr371Phe) SNV Pathogenic 13592 rs121918026 GRCh37: 6:132186026-132186026
GRCh38: 6:131864886-131864886
6 ENPP1 NM_006208.3(ENPP1):c.783C>G (p.Tyr261Ter) SNV Pathogenic 13597 rs267606784 GRCh37: 6:132179875-132179875
GRCh38: 6:131858735-131858735
7 ENPP1 ENPP1, 2-BP DEL, 878AA Deletion Pathogenic 13598 GRCh37:
GRCh38:
8 ENPP1 NM_006208.3(ENPP1):c.1612G>C (p.Asp538His) SNV Pathogenic 29843 rs387906673 GRCh37: 6:132195454-132195454
GRCh38: 6:131874314-131874314
9 ENPP1 NM_006208.3(ENPP1):c.795+1G>A SNV Pathogenic 29844 rs753851892 GRCh37: 6:132179888-132179888
GRCh38: 6:131858748-131858748
10 ENPP1 NM_006208.3(ENPP1):c.1756G>A (p.Gly586Arg) SNV Pathogenic 282087 rs777367269 GRCh37: 6:132198164-132198164
GRCh38: 6:131877024-131877024
11 ENPP1 NM_006208.3(ENPP1):c.1025G>T (p.Gly342Val) SNV Pathogenic 13591 rs121918025 GRCh37: 6:132182844-132182844
GRCh38: 6:131861704-131861704
12 ENPP1 NM_006208.3(ENPP1):c.1068G>A (p.Trp356Ter) SNV Pathogenic 692042 rs756541266 GRCh37: 6:132185688-132185688
GRCh38: 6:131864548-131864548
13 ENPP1 NM_006208.3(ENPP1):c.2677G>T (p.Glu893Ter) SNV Pathogenic 13585 rs121918023 GRCh37: 6:132211550-132211550
GRCh38: 6:131890410-131890410
14 ENPP1 NM_006208.3(ENPP1):c.797G>T (p.Gly266Val) SNV Pathogenic 13594 rs121908248 GRCh37: 6:132181528-132181528
GRCh38: 6:131860388-131860388
15 ENPP1 NM_006208.3(ENPP1):c.2101-2A>T SNV Pathogenic 807411 rs1585841844 GRCh37: 6:132203483-132203483
GRCh38: 6:131882343-131882343
16 ABCC6 NM_001171.5(ABCC6):c.1552C>T (p.Arg518Ter) SNV Pathogenic 30339 rs72650700 GRCh37: 16:16284104-16284104
GRCh38: 16:16190247-16190247
17 ABCC6 NM_001171.5(ABCC6):c.3940C>T (p.Arg1314Trp) SNV Pathogenic 6564 rs63750759 GRCh37: 16:16248831-16248831
GRCh38: 16:16154974-16154974
18 ABCC6 NM_001171.5(ABCC6):c.2294G>A (p.Arg765Gln) SNV Pathogenic 30337 rs67561842 GRCh37: 16:16272776-16272776
GRCh38: 16:16178919-16178919
19 ABCC6 NM_001171.5(ABCC6):c.4216C>A (p.Gln1406Lys) SNV Pathogenic 30338 rs387906859 GRCh37: 16:16244622-16244622
GRCh38: 16:16150765-16150765
20 ABCC6 NM_001171.5(ABCC6):c.2787+1G>T SNV Pathogenic 6560 rs72664209 GRCh37: 16:16267140-16267140
GRCh38: 16:16173283-16173283
21 ABCC6 NM_001171.5(ABCC6):c.3904G>A (p.Gly1302Arg) SNV Pathogenic 6579 rs63749856 GRCh37: 16:16248867-16248867
GRCh38: 16:16155010-16155010
22 ABCC6 NM_001171.5(ABCC6):c.3412C>T (p.Arg1138Trp) SNV Pathogenic 6571 rs28939701 GRCh37: 16:16256944-16256944
GRCh38: 16:16163087-16163087
23 ABCC6 NM_001171.5(ABCC6):c.2787+1G>T SNV Pathogenic 6560 rs72664209 GRCh37: 16:16267140-16267140
GRCh38: 16:16173283-16173283
24 ABCC6 NM_001171.5(ABCC6):c.1553G>A (p.Arg518Gln) SNV Pathogenic 265018 rs72653772 GRCh37: 16:16284103-16284103
GRCh38: 16:16190246-16190246
25 ENPP1 NM_006208.3(ENPP1):c.556G>C (p.Gly186Arg) SNV Pathogenic 988599 GRCh37: 6:132172407-132172407
GRCh38: 6:131851267-131851267
26 ABCC6 NM_001171.5(ABCC6):c.1999del (p.Ala667fs) Deletion Pathogenic 433256 rs72664227 GRCh37: 16:16276732-16276732
GRCh38: 16:16182875-16182875
27 ABCC6 NM_001171.6(ABCC6):c.615_616dup (p.Thr206fs) Microsatellite Pathogenic 998293 GRCh37: 16:16306087-16306088
GRCh38: 16:16212230-16212231
28 ABCC6 NM_001171.5(ABCC6):c.3736-1G>A SNV Pathogenic 6574 rs63750273 GRCh37: 16:16251667-16251667
GRCh38: 16:16157810-16157810
29 ENPP1 NM_006208.3(ENPP1):c.913C>A (p.Pro305Thr) SNV Pathogenic 29842 rs374270497 GRCh37: 6:132181644-132181644
GRCh38: 6:131860504-131860504
30 ABCC6 NM_001171.5(ABCC6):c.3421C>T (p.Arg1141Ter) SNV Pathogenic 6559 rs72653706 GRCh37: 16:16256935-16256935
GRCh38: 16:16163078-16163078
31 ABCC6 NM_001171.5(ABCC6):c.450dup (p.Ala151fs) Duplication Pathogenic 30340 rs387906860 GRCh37: 16:16313434-16313435
GRCh38: 16:16219577-16219578
32 ENPP1 NM_006208.3(ENPP1):c.1441C>T (p.Arg481Trp) SNV Pathogenic 547983 rs373044722 GRCh37: 6:132194066-132194066
GRCh38: 6:131872926-131872926
33 ABCC6 NM_001171.5(ABCC6):c.3421C>T (p.Arg1141Ter) SNV Pathogenic 6559 rs72653706 GRCh37: 16:16256935-16256935
GRCh38: 16:16163078-16163078
34 ABCC6 NM_001171.6(ABCC6):c.2071-1G>A SNV Pathogenic 1033352 GRCh37: 16:16276446-16276446
GRCh38: 16:16182589-16182589
35 ABCC6 NM_001171.5(ABCC6):c.3490C>T (p.Arg1164Ter) SNV Pathogenic 6572 rs72653744 GRCh37: 16:16256866-16256866
GRCh38: 16:16163009-16163009
36 ABCC6 NM_001171.6(ABCC6):c.3900del (p.Thr1301fs) Deletion Pathogenic 1033354 GRCh37: 16:16248871-16248871
GRCh38: 16:16155014-16155014
37 ENPP1 NM_006208.3(ENPP1):c.1006del (p.Ile336fs) Deletion Pathogenic 1034253 GRCh37: 6:132182825-132182825
GRCh38: 6:131861685-131861685
38 ENPP1 NM_006208.3(ENPP1):c.1441C>T (p.Arg481Trp) SNV Pathogenic/Likely pathogenic 547983 rs373044722 GRCh37: 6:132194066-132194066
GRCh38: 6:131872926-131872926
39 ABCC6 NM_001171.6(ABCC6):c.3892G>A (p.Val1298Ile) SNV Likely pathogenic 930520 GRCh37: 16:16248879-16248879
GRCh38: 16:16155022-16155022
40 ABCC6 NM_001171.6(ABCC6):c.2836del (p.Leu946fs) Deletion Likely pathogenic 930527 GRCh37: 16:16263662-16263662
GRCh38: 16:16169805-16169805
41 ABCC6 NM_001171.5(ABCC6):c.2097G>T (p.Glu699Asp) SNV Likely pathogenic 433259 rs72653784 GRCh37: 16:16276419-16276419
GRCh38: 16:16182562-16182562
42 ENPP1 NM_006208.3(ENPP1):c.1000C>G (p.Pro334Ala) SNV Likely pathogenic 634992 rs1562523328 GRCh37: 6:132182819-132182819
GRCh38: 6:131861679-131861679
43 ENPP1 NM_006208.3(ENPP1):c.323G>T (p.Cys108Phe) SNV Likely pathogenic 547984 rs763922486 GRCh37: 6:132171139-132171139
GRCh38: 6:131849999-131849999
44 ENPP1 NM_006208.3(ENPP1):c.1769G>A (p.Ser590Asn) SNV Likely pathogenic 870410 GRCh37: 6:132198177-132198177
GRCh38: 6:131877037-131877037
45 ENPP1 NM_006208.3(ENPP1):c.2376T>A (p.Asn792Lys) SNV Likely pathogenic 870422 GRCh37: 6:132206135-132206135
GRCh38: 6:131884995-131884995
46 ENPP1 NM_006208.3(ENPP1):c.2462G>A (p.Arg821His) SNV Conflicting interpretations of pathogenicity 788102 rs367759638 GRCh37: 6:132207719-132207719
GRCh38: 6:131886579-131886579
47 ABCC6 NM_001171.6(ABCC6):c.1214C>T (p.Ala405Val) SNV Uncertain significance 1030271 GRCh37: 16:16292002-16292002
GRCh38: 16:16198145-16198145
48 ABCC6 NM_001171.5(ABCC6):c.1108A>G (p.Asn370Asp) SNV Uncertain significance 433220 rs72653760 GRCh37: 16:16295926-16295926
GRCh38: 16:16202069-16202069
49 ENPP1 NM_006208.3(ENPP1):c.313+9_313+10insGGTG Insertion Uncertain significance 355327 rs536901634 GRCh37: 6:132168996-132168997
GRCh38: 6:131847856-131847857
50 ENPP1 NM_006208.3(ENPP1):c.1652A>G (p.Tyr551Cys) SNV Uncertain significance 561004 rs753071702 GRCh37: 6:132196932-132196932
GRCh38: 6:131875792-131875792

Expression for Arterial Calcification of Infancy

Search GEO for disease gene expression data for Arterial Calcification of Infancy.

Pathways for Arterial Calcification of Infancy

Pathways related to Arterial Calcification of Infancy according to KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230
2 Starch and sucrose metabolism hsa00500
3 Riboflavin metabolism hsa00740
4 Nicotinate and nicotinamide metabolism hsa00760
5 Pantothenate and CoA biosynthesis hsa00770
6 Metabolic pathways hsa01100

GO Terms for Arterial Calcification of Infancy

Cellular components related to Arterial Calcification of Infancy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.92 SPP1 KL FGF23 FAM20C ENPP1 ALPL
2 apical plasma membrane GO:0016324 9.71 SLC34A3 KL ENPP3 ABCC6
3 extracellular region GO:0005576 9.7 SPP1 MGP KL FGF23 FAM20C ENPP3
4 extracellular matrix GO:0031012 9.67 PHOSPHO1 MGP ALPL AHSG
5 endoplasmic reticulum lumen GO:0005788 9.65 SPP1 FGF23 FAM20C ARSJ AHSG
6 extracellular exosome GO:0070062 9.36 SPP1 SLC20A2 NT5E MGP KL GALNT3
7 extracellular membrane-bounded organelle GO:0065010 9.16 PHOSPHO1 ALPL

Biological processes related to Arterial Calcification of Infancy according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 post-translational protein modification GO:0043687 9.89 SPP1 FGF23 FAM20C AHSG
2 cellular protein metabolic process GO:0044267 9.85 SPP1 FGF23 FAM20C AHSG
3 skeletal system development GO:0001501 9.8 PHEX ANKH ALPL AHSG
4 ossification GO:0001503 9.76 SPP1 MGP AHSG
5 fibroblast growth factor receptor signaling pathway GO:0008543 9.73 KL GALNT3 FGF23
6 ATP metabolic process GO:0046034 9.65 FAM20C ENPP3 ENPP1
7 phosphate-containing compound metabolic process GO:0006796 9.61 FGF23 ENPP3 ENPP1
8 phosphate ion transmembrane transport GO:0035435 9.58 SLC20A2 ANKH
9 response to vitamin D GO:0033280 9.58 SPP1 PHEX ALPL
10 cellular response to vitamin D GO:0071305 9.57 PHEX FGF23
11 biomineral tissue development GO:0031214 9.55 SPP1 PHEX FAM20C ENPP1 ALPL
12 cellular response to parathyroid hormone stimulus GO:0071374 9.54 PHEX FGF23
13 negative regulation of bone mineralization GO:0030502 9.54 FGF23 ENPP1 AHSG
14 nucleoside triphosphate catabolic process GO:0009143 9.52 ENPP3 ENPP1
15 positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway GO:0090080 9.51 KL FGF23
16 phosphate ion transport GO:0006817 9.5 SLC34A3 SLC20A2 ANKH
17 response to sodium phosphate GO:1904383 9.46 PHEX FGF23
18 cellular phosphate ion homeostasis GO:0030643 9.43 SLC34A3 FGF23 ENPP1
19 inorganic diphosphate transport GO:0030505 9.26 ENPP3 ENPP1 ANKH ABCC6
20 regulation of bone mineralization GO:0030500 9.1 PHOSPHO1 MGP FGF23 ENPP1 ANKH AHSG

Molecular functions related to Arterial Calcification of Infancy according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.61 PHOSPHO1 PHEX NT5E KL ENPP3 ENPP1
2 fibroblast growth factor receptor binding GO:0005104 9.49 KL FGF23
3 sodium:phosphate symporter activity GO:0005436 9.48 SLC34A3 SLC20A2
4 NADH pyrophosphatase activity GO:0035529 9.46 ENPP3 ENPP1
5 pyrophosphatase activity GO:0016462 9.43 PHOSPHO1 ALPL
6 nucleotide diphosphatase activity GO:0004551 9.4 ENPP3 ENPP1
7 nucleoside-triphosphate diphosphatase activity GO:0047429 9.37 ENPP3 ENPP1
8 phosphodiesterase I activity GO:0004528 9.32 ENPP3 ENPP1
9 dTTP diphosphatase activity GO:0036218 9.26 ENPP3 ENPP1
10 inorganic phosphate transmembrane transporter activity GO:0005315 9.16 SLC20A2 ANKH
11 inorganic diphosphate transmembrane transporter activity GO:0030504 8.62 ANKH ABCC6

Sources for Arterial Calcification of Infancy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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