Chondrocalcinosis 2

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.

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.

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.

Chondrocalcinosis 2 is inherited in an autosomal dominant manner. 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.

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.

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:

• 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.

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.