Information on the following diseases can be found in the Related Disorders section of this report:

• Chondrocalcinosis Associated with Metabolic Disorders
• Gout
• Familial Apatite Crystal Deposition Disease

The symptoms of familial articular chondrocalcinosis usually begin as acute, recurring attacks of pain in a joint. These may include swelling, stiffness, and pain, usually confined to one joint and with little or no inflammation . A knee, wrist, hip or shoulder is most frequently affected, although any joint of the body may be involved. In a few cases, permanent fixation of a joint (ankylosis) has also been observed. Acute episodes can last for one day or up to several weeks, and symptoms may subside without treatment. Calcium deposits may accumulate around the bones of the spine (vertebrae) and cause back pain and/or loss of mobility. Generally, familial articular chondrocalcinosis is not as disabling or painful as classical gout, although in some cases, the symptoms may be as severe.

Chondrocalcinosis-2 (CCAL2) is a type of chondrocalcinosis in which there are absent or unnoticeable joint changes and chronic arthritis. Chondrocalcinosis-1 (CCAL1) is associated with early onset osteoarthritis.
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Studies indicate that symptoms of the disorder develop due to decreased activity of the enzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH). Attacks are caused by the release of calcium pyrophosphate crystals into the joint.

In most cases, familial articular chondrocalcinosis is inherited as an autosomal dominant genetic trait.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Two different genes have been linked to the two types of chondrocalcinosis. CCAL2 is caused by a mutation in the ANKH gene which is located on chromosome 5 at gene map locus 5p15.2-p14.1. The gene for CCAL1 has been mapped to the short arm of chromosome 8 (8q). The primary event causing CCAL1 has not been determined. It could be that a defect in a gene for chondrocalcinosis causes a deposition of calcium-containing crystals in the joint tissue that then leads to osteoarthritis. Alternatively, a mutation in an osteoarthritis gene may cause changes in cartilage allowing calcium-containing crystals to be more readily deposited.

The symptoms of familial articular chondrocalcinosis are thought to be more severe in those affected individuals who carry two of a pair of defective genes for this disorder (homozygotes). Those who have only one of a pair of the defective genes (heterozygotes) are thought to experience less severe symptoms.

A small number of cases of articular chondrocalcinosis appear to occur for no apparent reason (sporadic).
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Familial articular chondrocalcinosis is a rare disorder that typically affects adults over the age of 60 years. However, some cases have been reported in younger adults. The distribution of cases by sex is unclear. Some studies indicate a greater prevalence in females; other studies suggest that males are affected more frequently. All ethnic groups can be affected.
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Symptoms of the following disorders can be similar to those of familial articular chondrocalcinosis. Comparisons may be useful for a differential diagnosis:

Chondrocalcinosis may also occur in association with certain metabolic conditions such as hyperparathyroidism, familial hypocalciuric hypercalcemia, Wilson's Disease, Bartter's Syndrome, hypophosphatasia, hypomagnesemia, myxedematous hypothyroidism, ochronosis, or hereditary hemochromatosis. Surgical procedures and trauma may also play a role in causing chondrocalcinosis. The symptoms are similar to those of classical gout and may include swelling, stiffness, and pain of one or more joints of the body. Fever and chills are also common during acute attacks. (For more information on these diseases, choose "Wilson," "Bartter," "hypophosphatasia," "hypothyroidism," and "hereditary hemochromatosis” as your search terms in the Rare Disease Database.)

Gout is a common metabolic disorder characterized by an inborn error of uric acid (purine) metabolism. Excessive uric acid may form crystals (sodium urate) that are deposited in the kidney, joints, and other areas of the body. The large toe is the most common site for the accumulation of crystals. Symptoms may include sharp pain in the toe or other affected area, joint swelling and pain, chills, and/or fever. The symptoms recur with episodes becoming longer in duration each year. If left untreated, destructive changes may develop in the joints and kidneys.

Familial apatite crystal deposition disease is a rare inherited metabolic disorder characterized by deposits of carbonate calcium hydroxyapatite in the joints. Symptoms may include morning stiffness, pain, and limited mobility due to crystal accumulation in the spine. Pain may also occur in the area of the ribs (costochondral) and in the small joints of the hands. Familial apatite crystal deposition disease is inherited as an autosomal dominant genetic trait.
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Diagnosis
Few or no symptoms may be apparent in the first several decades of life. X-rays of joints, especially the knees and wrists, may detect calcifications before symptoms occur. The diagnosis of familial articular chondrocalcinosis is based on a clinical evaluation that includes a thorough patient history and specialized laboratory tests. In one test, fluid is removed from around an affected joint (synovial fluid). The presence of calcium pyrophosphate crystals in this fluid confirms the diagnosis of articular chondrocalcinosis. Radiographic (x-ray) studies typically demonstrate calcium deposits in the cartilage around joints (articular).

Treatment
Treatment for familial articular chondrocalcinosis is symptomatic. There is no way to prevent the formation of calcium pyrophosphate crystals or to satisfactorily remove existing crystals from the joints.

Acute attacks of familial articular chondrocalcinosis are treated in several ways. Excess fluid may be drained from the affected joint by means of syringe. If only one joint is involved, a corticosteroid drug (i.e., prednisone) may be injected directly into the affected joint (intra- articular). For those individuals with frequent, recurring acute attacks, colchicine may be an effective drug for treating familial articular chondrocalcinosis. This medication is also used to treat classical gout. Other drugs that are frequently used to treat joint pain include aspirin and other nonsteroidal antiinflammatory drugs (e.g., ibuprofen and naproxen sodium) that are commonly prescribed for many types of arthritic conditions.

During an acute attack of familial articular chondrocalcinosis, the affected joint may require rest. Splints, canes, and other devices that protect and support the joint may be prescribed and may require special fitting. Once the episode subsides, or in cases of the milder chronic form, rest should be balanced with appropriate exercise that is carefully monitored by a physician or physical therapist.

In some rare cases of familial articular chondrocalcinosis, surgery may be necessary to repair a joint that is badly damaged, very painful and unstable or immobile. Surgery may be an effective means for reducing pain and enhancing mobility in some cases.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Research is ongoing to investigate new treatments for familial articular chondrocalcinosis. The drug adrenocorticotropic hormone (ACTH) is being tested as a treatment for those patients with all forms of chondrocalcinosis who also have multiple medical problems. More studies are needed to determine the long-term safety and effectiveness of ACTH for the treatment of articular chondrocalcinosis.

Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.

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Ryan LM, McCarthy DJ. Calcium pyrophosphate crystal deposition disease, pseudogout, and articular chondrocalcinocic. In: Koopman, ed. Arthritis and allied conditions: a textbook of rheumatology, 13th ed. Baltimore: Williams and Wilkins, 1997:2103-2125.

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