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Arterial calcification, generalized, of infancy, 1(GACI1)

MedGen UID:
1631685
Concept ID:
C4551985
Disease or Syndrome
Synonyms: Arterial Calcification, Generalized, of Infancy; GACI1; Idiopathic infantile arterial calcification; Occlusive infantile arteriopathy
 
Gene (location): ENPP1 (6q23.2)
 
Monarch Initiative: MONDO:0008817
OMIM®: 208000

Disease characteristics

Excerpted from the GeneReview: Generalized Arterial Calcification of Infancy
Generalized arterial calcification of infancy (GACI) is characterized by infantile onset of widespread arterial calcification and/or narrowing of large and medium-sized vessels resulting in cardiovascular findings (which can include heart failure, respiratory distress, edema, cyanosis, hypertension, and/or cardiomegaly). Additional findings can include typical skin and retinal manifestations of pseudoxanthoma elasticum (PXE), periarticular calcifications, development of rickets after infancy, cervical spine fusion, and hearing loss. While mortality in infancy is high, survival into the third and fourth decades has occurred. [from GeneReviews]
Authors:
Shira G Ziegler  |  William A Gahl  |  Carlos R Ferreira   view full author information

Clinical features

From HPO
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Myocardial infarction
MedGen UID:
10150
Concept ID:
C0027051
Disease or Syndrome
Necrosis of the myocardium caused by an obstruction of the blood supply to the heart and often associated with chest pain, shortness of breath, palpitations, and anxiety as well as characteristic EKG findings and elevation of serum markers including creatine kinase-MB fraction and troponin.
Renal artery stenosis
MedGen UID:
19727
Concept ID:
C0035067
Disease or Syndrome
The presence of stenosis of the renal artery.
Arterial stenosis
MedGen UID:
11612
Concept ID:
C0038449
Pathologic Function
Narrowing or constriction of the inner surface (lumen) of an artery.
Coronary artery calcification
MedGen UID:
345985
Concept ID:
C1611184
Pathologic Function
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in a coronary artery.
Generalized arterial calcification
MedGen UID:
870812
Concept ID:
C4025269
Pathologic Function
Calcification, that is, pathological deposition of calcium salts, affecting arteries distributed throughout the body.
Carotid artery calcification
MedGen UID:
1617566
Concept ID:
C4285890
Disease or Syndrome
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in a carotid artery.
Abdominal aortic calcification
MedGen UID:
1611250
Concept ID:
C4531207
Finding
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in abdominal aorta.
Growth abnormality
MedGen UID:
808205
Concept ID:
C0262361
Finding
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Ankylosis
MedGen UID:
8101
Concept ID:
C0003090
Pathologic Function
A reduction of joint mobility resulting from changes involving the articular surfaces.
Periarticular calcification
MedGen UID:
575157
Concept ID:
C0342650
Disease or Syndrome
Calcified deposits in soft tissue structures outside a joint.
Hypophosphatemic rickets
MedGen UID:
309957
Concept ID:
C1704375
Disease or Syndrome
Rickets due to low serum phosphate concentrations, the cause of which can be nutritional or genetic. This condition is characterized by normal parathyroid hormone concentrations, usually caused by renal phosphate wasting occurring in isolation or as part of a renal tubular disorder, and characterized by resistance to treatment with ultraviolet radiation or vitamin D.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Fetal distress
MedGen UID:
5164
Concept ID:
C0015930
Pathologic Function
An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

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
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
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

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
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
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
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
Nitschke Y, Rutsch F
Curr Osteoporos Rep 2017 Aug;15(4):255-270. doi: 10.1007/s11914-017-0370-3. PMID: 28585220

Diagnosis

Khursigara G, Huertas P, Wenkert D, O'Brien K, Sabbagh Y
Bone 2023 Jun;171:116750. Epub 2023 Mar 30 doi: 10.1016/j.bone.2023.116750. PMID: 37003563
Mercurio SA, Chunn LM, Khursigara G, Nester C, Wray K, Botschen U, Kiel MJ, Rutsch F, Ferreira CR
Hum Mutat 2022 Dec;43(12):1673-1705. Epub 2022 Oct 8 doi: 10.1002/humu.24477. PMID: 36150100
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
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
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

Khursigara G, Huertas P, Wenkert D, O'Brien K, Sabbagh Y
Bone 2023 Jun;171:116750. Epub 2023 Mar 30 doi: 10.1016/j.bone.2023.116750. PMID: 37003563
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
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT
Clin Transl Sci 2021 Jan;14(1):362-372. Epub 2020 Oct 20 doi: 10.1111/cts.12887. PMID: 33064927Free PMC Article
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
Khan T, Sinkevicius KW, Vong S, Avakian A, Leavitt MC, Malanson H, Marozsan A, Askew KL
Dis Model Mech 2018 Oct 8;11(10) doi: 10.1242/dmm.035691. PMID: 30158213Free PMC Article

Prognosis

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
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
Federici D, Torii S, Ciuffreda M, Galletti L, Lorini L, Bonanomi E, Gianatti A, Iascone M, Park J, Guo L, Romero ME, Kolodgie FD, Guagliumi G, Virmani R
Cardiovasc Pathol 2018 Sep-Oct;36:15-19. Epub 2018 May 18 doi: 10.1016/j.carpath.2018.05.001. PMID: 30005391
Brunod I, Tosello B, Hassid S, Gire C, Thomachot L, Panuel M
BMC Pediatr 2018 Jul 5;18(1):217. doi: 10.1186/s12887-018-1198-4. PMID: 29976176Free PMC Article
Van Reempts PJ, Boven KJ, Spitaels SE, Roodhooft AM, Vercruyssen EL, Van Acker KJ
Calcif Tissue Int 1991 Jan;48(1):1-6. doi: 10.1007/BF02555789. PMID: 2007222

Clinical prediction guides

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
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
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
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
Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, Le Merrer M, Guest G, Lambot K, Tazarourte-Pinturier MF, Chassaing N, Roche O, Feenstra I, Loechner K, Deshpande C, Garber SJ, Chikarmane R, Steinmann B, Shahinyan T, Martorell L, Davies J, Smith WE, Kahler SG, McCulloch M, Wraige E, Loidi L, Höhne W, Martin L, Hadj-Rabia S, Terkeltaub R, Rutsch F
Am J Hum Genet 2012 Jan 13;90(1):25-39. Epub 2011 Dec 29 doi: 10.1016/j.ajhg.2011.11.020. PMID: 22209248Free PMC Article

Recent systematic reviews

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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