Rare Rheumatology News

Disease Profile

Arterial calcification of infancy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

Q28.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Occlusive infantile arteriopathy; Idiopathic infantile arterial calcification; IIAC;

Categories

Blood Diseases; Congenital and Genetic Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

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 endorgan 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.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Hypophosphatemic rickets
0004912
Periarticular calcification
0025477
Short stature
Decreased body height
Small stature

[ more ]

0004322
Percent of people who have these symptoms is not available through HPO
Ankylosis
0031013
Arterial stenosis
Narrowing of an artery
0100545
Autosomal recessive inheritance
0000007
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Coronary artery calcification
0001717
Generalized arterial calcification
0004940
Growth abnormality
Abnormal growth
Growth issue

[ more ]

0001507
Hypertension
0000822
Myocardial infarction
Heart attack
0001658

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Arterial calcification of infancy. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Arterial calcification of infancy. Click on the link to view a sample search on this topic.