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Arterial calcification of infancy(IIAC)

MedGen UID:
395331
•Concept ID:
C1859727
•
Disease or Syndrome
Synonyms: Generalized arterial calcification in infancy; Generalized arterial calcification of infancy
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (Orphanet)
Autosomal dominant inheritance (Orphanet)
 
Related genes: ENPP1, ABCC6
 
Monarch Initiative: MONDO:0018870
OMIM®: 208000
OMIM® Phenotypic series: PS208000
Orphanet: ORPHA51608

Definition

Generalized arterial calcification of infancy (GACI) is a severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. GACI is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure (summary by Rutsch et al., 2003 and Cheng et al., 2005). Genetic Heterogeneity of Arterial Calcification Generalized arterial calcification of infancy-2 (GACI2; 614473) is caused by mutation in the ABCC6 gene (603234) on chromosome 16p13. Homozygous or compound heterozygous mutation in the NT5E gene (129190) can cause adult-onset of calcification of arteries and joints (211800). [from OMIM]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Prenatal diagnosis of generalized arterial calcification of infancy in the second trimester.
Pu L, Dai X, Liu H, Li L, Zhao F, Chen J
Prenat Diagn 2022 Nov;42(12):1538-1544. Epub 2022 Oct 5 doi: 10.1002/pd.6245. PMID: 36184779
Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management.
Boyce AM, Gafni RI, Ferreira CR
Curr Osteoporos Rep 2020 Jun;18(3):232-241. doi: 10.1007/s11914-020-00577-4. PMID: 32172442Free PMC Article
Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts.
Nitschke Y, Rutsch F
Curr Osteoporos Rep 2017 Aug;15(4):255-270. doi: 10.1007/s11914-017-0370-3. PMID: 28585220

Recent clinical studies

Etiology

Prenatal diagnosis of generalized arterial calcification of infancy in the second trimester.
Pu L, Dai X, Liu H, Li L, Zhao F, Chen J
Prenat Diagn 2022 Nov;42(12):1538-1544. Epub 2022 Oct 5 doi: 10.1002/pd.6245. PMID: 36184779
Longitudinal assessment of vascular calcification in generalized arterial calcification of infancy.
Ramirez-Suarez KI, Cohen SA, Barrera CA, Levine MA, Goldberg DJ, Otero HJ
Pediatr Radiol 2022 Nov;52(12):2329-2341. Epub 2022 Apr 19 doi: 10.1007/s00247-022-05364-0. PMID: 35438330Free PMC Article
Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies.
Ferreira CR, Kintzinger K, Hackbarth ME, Botschen U, Nitschke Y, Mughal MZ, Baujat G, Schnabel D, Yuen E, Gahl WA, Gafni RI, Liu Q, Huertas P, Khursigara G, Rutsch F
J Bone Miner Res 2021 Nov;36(11):2193-2202. Epub 2021 Aug 16 doi: 10.1002/jbmr.4418. PMID: 34355424Free PMC Article
Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management.
Boyce AM, Gafni RI, Ferreira CR
Curr Osteoporos Rep 2020 Jun;18(3):232-241. doi: 10.1007/s11914-020-00577-4. PMID: 32172442Free PMC Article
Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts.
Nitschke Y, Rutsch F
Curr Osteoporos Rep 2017 Aug;15(4):255-270. doi: 10.1007/s11914-017-0370-3. PMID: 28585220

Diagnosis

Generalized Arterial Calcification of Infancy (GACI).
Baujat G, Besançon A
Arch Pediatr 2024 Sep;31(4S1):4S21-4S26. doi: 10.1016/S0929-693X(24)00153-2. PMID: 39343469
Prenatal diagnosis of generalized arterial calcification of infancy in the second trimester.
Pu L, Dai X, Liu H, Li L, Zhao F, Chen J
Prenat Diagn 2022 Nov;42(12):1538-1544. Epub 2022 Oct 5 doi: 10.1002/pd.6245. PMID: 36184779
Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI).
Theng EH, Brewer CC, Oheim R, Zalewski CK, King KA, Delsmann MM, Rolvien T, Gafni RI, Braddock DT, Jeffrey Kim H, Ferreira CR
Orphanet J Rare Dis 2022 Jul 19;17(1):273. doi: 10.1186/s13023-022-02410-w. PMID: 35854274Free PMC Article
Longitudinal assessment of vascular calcification in generalized arterial calcification of infancy.
Ramirez-Suarez KI, Cohen SA, Barrera CA, Levine MA, Goldberg DJ, Otero HJ
Pediatr Radiol 2022 Nov;52(12):2329-2341. Epub 2022 Apr 19 doi: 10.1007/s00247-022-05364-0. PMID: 35438330Free PMC Article
Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies.
Ferreira CR, Kintzinger K, Hackbarth ME, Botschen U, Nitschke Y, Mughal MZ, Baujat G, Schnabel D, Yuen E, Gahl WA, Gafni RI, Liu Q, Huertas P, Khursigara G, Rutsch F
J Bone Miner Res 2021 Nov;36(11):2193-2202. Epub 2021 Aug 16 doi: 10.1002/jbmr.4418. PMID: 34355424Free PMC Article

Therapy

Longitudinal assessment of vascular calcification in generalized arterial calcification of infancy.
Ramirez-Suarez KI, Cohen SA, Barrera CA, Levine MA, Goldberg DJ, Otero HJ
Pediatr Radiol 2022 Nov;52(12):2329-2341. Epub 2022 Apr 19 doi: 10.1007/s00247-022-05364-0. PMID: 35438330Free PMC Article
Oral supplementation of inorganic pyrophosphate in pseudoxanthoma elasticum.
Kozák E, Fülöp K, Tőkési N, Rao N, Li Q, Terry SF, Uitto J, Zhang X, Becker C, Váradi A, Pomozi V
Exp Dermatol 2022 Apr;31(4):548-555. Epub 2021 Nov 17 doi: 10.1111/exd.14498. PMID: 34758173Free PMC Article
From membrane to mineralization: the curious case of the ABCC6 transporter.
Verschuere S, Van Gils M, Nollet L, Vanakker OM
FEBS Lett 2020 Dec;594(23):4109-4133. Epub 2020 Nov 21 doi: 10.1002/1873-3468.13981. PMID: 33131056
Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management.
Boyce AM, Gafni RI, Ferreira CR
Curr Osteoporos Rep 2020 Jun;18(3):232-241. doi: 10.1007/s11914-020-00577-4. PMID: 32172442Free PMC Article
Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders: Pathomechanisms and Treatment Development.
Li Q, van de Wetering K, Uitto J
Am J Pathol 2019 Feb;189(2):216-225. Epub 2018 Nov 7 doi: 10.1016/j.ajpath.2018.09.014. PMID: 30414410Free PMC Article

Prognosis

Generalized Arterial Calcification of Infancy (GACI).
Baujat G, Besançon A
Arch Pediatr 2024 Sep;31(4S1):4S21-4S26. doi: 10.1016/S0929-693X(24)00153-2. PMID: 39343469
Generalized Arterial Calcification of Infancy Mimicking Coarctation of Aorta in a Neonate.
Varghese NA, Gopal BR, Maheswaran A, Raju V, Vijayaraghavan A
Radiol Cardiothorac Imaging 2024 Jun;6(3):e230403. doi: 10.1148/ryct.230403. PMID: 38900025Free PMC Article
Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies.
Ferreira CR, Kintzinger K, Hackbarth ME, Botschen U, Nitschke Y, Mughal MZ, Baujat G, Schnabel D, Yuen E, Gahl WA, Gafni RI, Liu Q, Huertas P, Khursigara G, Rutsch F
J Bone Miner Res 2021 Nov;36(11):2193-2202. Epub 2021 Aug 16 doi: 10.1002/jbmr.4418. PMID: 34355424Free PMC Article
Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI).
Ferreira CR, Hackbarth ME, Ziegler SG, Pan KS, Roberts MS, Rosing DR, Whelpley MS, Bryant JC, Macnamara EF, Wang S, Müller K, Hartley IR, Chew EY, Corden TE, Jacobsen CM, Holm IA, Rutsch F, Dikoglu E, Chen MY, Mughal MZ, Levine MA, Gafni RI, Gahl WA
Genet Med 2021 Feb;23(2):396-407. Epub 2020 Oct 2 doi: 10.1038/s41436-020-00983-0. PMID: 33005041Free PMC Article
Idiopathic Arterial Calcification of Infancy: Case Report.
Attia TH, Abd Alhamed MM, Selim MF, Haggag MS, Fathalla D
J Radiol Case Rep 2015 Nov;9(11):32-40. Epub 2015 Nov 30 doi: 10.3941/jrcr.v9i11.2622. PMID: 27252793Free PMC Article

Clinical prediction guides

Bone Marrow-Derived ABCC6 Is an Essential Regulator of Ectopic Calcification In Pseudoxanthoma Elasticum.
Brampton C, Pomozi V, Le Corre Y, Zoll J, Kauffenstein G, Ma C, Hoffmann PR, Martin L, Le Saux O
J Invest Dermatol 2024 Aug;144(8):1772-1783.e3. Epub 2024 Feb 15 doi: 10.1016/j.jid.2024.01.026. PMID: 38367909Free PMC Article
INZ-701 Prevents Ectopic Tissue Calcification and Restores Bone Architecture and Growth in ENPP1-Deficient Mice.
Cheng Z, O'Brien K, Howe J, Sullivan C, Schrier D, Lynch A, Jungles S, Sabbagh Y, Thompson D
J Bone Miner Res 2021 Aug;36(8):1594-1604. Epub 2021 May 5 doi: 10.1002/jbmr.4315. PMID: 33900645
Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI).
Ferreira CR, Hackbarth ME, Ziegler SG, Pan KS, Roberts MS, Rosing DR, Whelpley MS, Bryant JC, Macnamara EF, Wang S, Müller K, Hartley IR, Chew EY, Corden TE, Jacobsen CM, Holm IA, Rutsch F, Dikoglu E, Chen MY, Mughal MZ, Levine MA, Gafni RI, Gahl WA
Genet Med 2021 Feb;23(2):396-407. Epub 2020 Oct 2 doi: 10.1038/s41436-020-00983-0. PMID: 33005041Free PMC Article
Insights into dental mineralization from three heritable mineralization disorders.
Chavez MB, Kramer K, Chu EY, Thumbigere-Math V, Foster BL
J Struct Biol 2020 Oct 1;212(1):107597. Epub 2020 Aug 3 doi: 10.1016/j.jsb.2020.107597. PMID: 32758526Free PMC Article
Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders: Pathomechanisms and Treatment Development.
Li Q, van de Wetering K, Uitto J
Am J Pathol 2019 Feb;189(2):216-225. Epub 2018 Nov 7 doi: 10.1016/j.ajpath.2018.09.014. PMID: 30414410Free PMC Article

Recent systematic reviews

Antenatal diagnosis of idiopathic arterial calcification: a systematic review with a report of two cases.
Mastrolia SA, Weintraub AY, Baron J, Sciaky-Tamir Y, Koifman A, Loverro G, Hershkovitz R
Arch Gynecol Obstet 2015 May;291(5):977-86. Epub 2014 Dec 19 doi: 10.1007/s00404-014-3567-z. PMID: 25524533

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