Rare Immunology News

Disease Profile

Chondrocalcinosis 2

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

Adult

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ICD-10

M11.1

Inheritance

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

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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

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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.

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

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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.

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Not applicable

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Other names (AKA)

CCAL2; Chondrocalcinosis familial articular; Familial articular chondrocalcinosis;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases

Summary

Chondrocalcinosis 2 is a rare disease characterized by the accumulation of calcium pyrophosphate dihydrate (CPP) crystals in and around the joints. A buildup of these crystals can lead to joint pain and damage that is progressive (worsens over time).[1][2] Signs and symptoms of the disease include chronic joint pain or sudden, recurrent episodes of pain, as well as stiffness or swelling of the joints.[1][2][3] Chondrocalcinosis 2 is actually a familial form of chondrocalcinosis (also known as calcium pyrophosphate deposition disease or CPPD), which is caused by a similar buildup of CPP crystals but is associated with the aging process. The age-related chondrocalcinosis is quite common, whereas chondrocalcinosis 2 is not.[4] In addition, people with chondrocalcinosis 2 are more likely to have symptoms that develop earlier in adulthood than the age-related form.[3].

Chondrocalcinosis 2 is caused by changes in the ANKH gene. The disease is inherited in an autosomal dominant manner.[2][4] Chondrocalcinosis 2 is diagnosed based on imaging such as X-rays. The diagnosis can be confirmed with genetic testing of the ANKH gene. Treatment may include the use of corticosteroids, pain relievers, and physical therapy.[1][2]

Symptoms

Some people with chondrocalcinosis 2 may not have any symptoms of the disease other than showing calcium deposits in and around joints on X-rays. Others may experience symptoms such as joint pain and swelling and difficulty moving the joints. These symptoms can be similar to the symptoms of arthritis or gout, and they may be described as “pseudoarthritis” or “pseudogout.”[1]

The symptoms can be chronic (occurring all the time) or may occur in sudden episodes. If the pain occurs in episodes, it can last anywhere from several hours to several weeks.[2][3] In some cases, episodes of pain may cause fevers.[5] The attack may affect only one joint or multiple joints. Joints that are most commonly affected include the knees, wrists, hips, or shoulders.[1][2] Some people with chondrocalcinosis 2 may experience pain in the back if calcium deposits develop around the bones of the spine.[2][3]

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
80%-99% of people have these symptoms
Abnormality of the intervertebral disk
0005108
Arthralgia
Joint pain
0002829
Calcification of cartilage
0100593
Joint swelling
0001386
30%-79% of people have these symptoms
Osteoarthritis
Degenerative joint disease
0002758
5%-29% of people have these symptoms
Chondrocalcinosis
Calcium deposits in joints
0000934
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Arthropathy
Disease of the joints
0003040
Autosomal dominant inheritance
0000006
Polyarticular chondrocalcinosis
0005017

Cause

Chondrocalcinosis 2 is caused by changes in the ANKH gene. When a genetic change causes a disease, it is also known as a pathogenic variation. The ANKH gene provides instructions to make a protein that may interact with or regulate other proteins involved in the controlling the formation of calcium pyrophosphate (CPP) mineralization. Mineralization is the process by which calcium and phosphorus form crystals to become part of the bone structure. Although the exact function of the ANKH protein is not known, it is known that the pathogenic variation in the ANKH gene allows too many CPP crystals to build up in the cartilage of joints. The buildup of crystals weakens the cartilage and causes it to break down more easily, leading to the joint pain and other symptoms associated with chondrocalcinosis 2.[1][6]

Diagnosis

A diagnosis of chondrocalcinosis 2 is often suspected based on signs and symptoms of the disease, as well as the age the symptoms begin. Doctors may wish to take a thorough personal and family history to evaluate for other possible causes of chondrocalcinosis and to determine if there are other family members who may be affected. Specialized testing, such as analysis of the fluid in the joints (synovial fluid), can confirm the diagnosis. X-rays or other imaging techniques may also be used to identify calcium deposits in the cartilage of joints.[1][3]

If a doctor suspects that a person has chondrocalcinosis caused by a change (pathogenic variation) in the ANKH gene, genetic testing may be ordered to confirm the diagnosis and identify other family members who may have the same pathogenic variation.[1]

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.

    Treatment

    There is currently no cure for chondrocalcinosis 2. However, therapies are available to manage the signs and symptoms of the disease. During episodes of joint pain, stiffness, or swelling, the following treatments may be recommended to relieve symptoms:[1]

    For people who have frequent episodes of pain or for whom other medications are not effective, small doses of a medication called colchicine may be recommended. However, this medication has side effects and may not help everyone with chondrocalcinosis 2.[1]

    In some cases, people with chondrocalcinosis 2 may be required to wear a splint or brace to prevent too much movement. In other cases, physical therapy may be recommended for safe movement of the affected joint.[2][5]

    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 Chondrocalcinosis 2. This website is maintained by the National Library of Medicine.
      • The Merck Manual provides information on this condition for patients and caregivers.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Merck Manual for health care professionals provides information on Chondrocalcinosis 2.
        • 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 Chondrocalcinosis 2. Click on the link to view a sample search on this topic.

          References

          1. Saadeh CK and Davey-Ranasinghe N. Calcium Pyrophosphate Deposition Disease. Medscape Reference. November 28, 2017; https://emedicine.medscape.com/article/330936-overview.
          2. Chondrocalcinosis, Familial Articular. National Organization for Rare Disorders (NORD). 2003; https://rarediseases.org/rare-diseases/chondrocalcinosis-familial-articular/.
          3. Bardin T and Richette P. Familial calcium pyrophosphate deposition. Orphanet. December 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1416.
          4. Chondrocalcinosis 2; CCAL2. Online Mendelian Inheritance in Man (OMIM). March 4, 2015; https://www.omim.org/entry/118600.
          5. Ryan LM. Calcium Pyrophosphate Arthritis. Merck Manual: Consumer Version. https://www.merckmanuals.com/home/bone,-joint,-and-muscle-disorders/gout-and-pseudogout/calcium-pyrophosphate-arthritis. Accessed 12/26/2017.
          6. Williams CJ. The role of ANKH in pathologic mineralization of cartilage.. Curr Opin Rheumatol. March 2016; 28(2):145-51. https://www.ncbi.nlm.nih.gov/pubmed/26599446.

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