Arterial Calcification of Infancy

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Disease Ontology 12 DOID:0050644 KEGG 38 H01002 MeSH 45 C537440 MESH via Orphanet 46 C537440

ICD10 via Orphanet 35 Q28.8 UMLS via Orphanet 75 C0264955 C1859727 Orphanet 60 ORPHA51608 UMLS 74 C1859727

NIH Rare Diseases : ⁵⁴ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 51608Disease definitionA 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.EpidemiologyApproximately 300 cases have been reported worldwide in the medical literature. Based on carrier frequency of the recognized pathogenic variants, the worldwide prevalence is estimated at 1/566,000.Clinical descriptionDisease 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.EtiologyCausal mutations have been identified in the genesENPP1 (chromosome 6q23.2) and ABCC6 (chromosome 16.13.11) 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 methodsDiagnosis 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 diagnosisDifferential 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 diagnosisAntenatal 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 counselingThe 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 treatmentUse 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.PrognosisPrognosis 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.Visit the Orphanet disease page for more resources.

MalaCards based summary : Arterial Calcification of Infancy, also known as generalized arterial calcification of infancy, is related to pseudoxanthoma elasticum and rickets. 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 skin, heart and testes, and related phenotypes are Decreased melanin production and cardiovascular system

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.

Wikipedia : ⁷⁷ Generalized arterial calcification of infancy (GACI) is an extremely rare, usually fatal genetic... more...

GeneReviews: NBK253403

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased melanin production	GR00056-A	8.62	FGF23 NT5E

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