Chondrocalcinosis 2

Title

Other Names:

CCAL2; Chondrocalcinosis familial articular; Familial articular chondrocalcinosis; CCAL2; Chondrocalcinosis familial articular; Familial articular chondrocalcinosis; Calcium pyrophosphate arthropathy; CPPDD; Familial Calcium pyrophosphate dihydrate deposition disease; Calcium gout; Calcium gout, familial; Calcium pyrophosphate arthropathy, familial; Pseudogout, familial See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases

Summary 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]

Last updated: 1/12/2018

Symptoms 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]

Last updated: 1/12/2018

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.

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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
Seizures	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

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Last updated: 1/1/2020

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Cause 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]

Last updated: 1/12/2018

Inheritance Inheritance

Chondrocalcinosis 2 is inherited in an autosomal dominant manner.^[4] This means that people with chondrocalcinosis 2 have a disease-causing change (pathogenic variation) in only one copy of the ANKH gene in each cell of the body. Most genes, including the ANKH gene, come in pairs, and a person inherits one copy of each gene from their mother and the other from their father.

When a person with chondrocalcinosis 2 has children, each child has a:

50% chance to inherit the changed copy of ANKH, meaning they may develop chondrocalcinosis 2
50% chance to inherit the working copy of ANKH, meaning they will not develop chondrocalcinosis 2

In some cases, a person with chondrocalcinosis 2 inherits the disease from an affected parent. In other cases, the pathogenic variation that causes the disease is new (de novo) in the affected person, and there is no history of the disease in the family. However, a person with a new pathogenic variation in the ANKH gene has a 50% chance of passing this disease-causing change on to each of his or her children.

Last updated: 1/12/2018

Diagnosis 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]

Last updated: 1/12/2018

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 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]

Joint aspiration (draining of fluid from the affected joint)
Corticosteroid injections
Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin or ibuprofen

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]

Last updated: 1/12/2018

Prognosis Prognosis

For some people with chondrocalcinosis 2, medications and other therapies work well to treat signs and symptoms of the disease. For others, the buildup of calcium pyrophosphate dehydrate (CPP) crystals is severe and can cause pain that is not relieved with treatment. At this time there is, unfortunately, no way to prevent or remove the buildup of CPP crystals in the joints. In some cases, the pain associated with chondrocalcinosis 2 can be severe and very disabling.^[1]^[3]

Last updated: 1/12/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes other genetic conditions causing secondary CC such as chronic hypomagnesaemia, Gitelman syndrome, rare hereditary hemochromatosis and hypophosphatasia (see these terms). CPPD can also occur sporadically but it is a separate, much more common entity, with aging being the most important risk factor. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Chondrocalcinosis 2. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations 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

Arthritis Foundation
1355 Peachtree St. NE
6th Floor
Atlanta, GA 30309
Toll-free: 1-844-571-HELP (4357)
Telephone: +1-404-872-7100
Website: https://www.arthritis.org

Do you know of an organization? We want to hear from you.

Learn More 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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Saadeh CK and Davey-Ranasinghe N. Calcium Pyrophosphate Deposition Disease. Medscape Reference. November 28, 2017; http://emedicine.medscape.com/article/330936-overview.
Chondrocalcinosis, Familial Articular. National Organization for Rare Disorders (NORD). 2003; https://rarediseases.org/rare-diseases/chondrocalcinosis-familial-articular/.
Bardin T and Richette P. Familial calcium pyrophosphate deposition. Orphanet. December 2013; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1416.
Chondrocalcinosis 2; CCAL2. Online Mendelian Inheritance in Man (OMIM). March 4, 2015; http://www.omim.org/entry/118600.
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.
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.