Familial articular chondrocalcinosis is a rare inherited metabolic disorder characterized by deposits of calcium pyrophosphate dihydrate crystals (CPPD) in one or more joint cartilages resulting in eventual damage to the joints. Symptoms may develop due to decreased activity of the enzyme nucleoside triphosphate pyrophosphohydrolase. The symptoms of familial articular chondrocalcinosis mimic those of classical gout and may include swelling, stiffness, and pain, usually in one joint. The knee is most commonly affected. Chondrocalcinosis occurs in a hereditary form (familial articular chondrocalcinosis), a form associated with metabolic disorders and a sporadic form. The hereditary forms are subdivided into chondrocalcinosis-1 (CCAL1) and chondrocalcinosis-2 (CCAL2).
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.
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).
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.
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 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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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry no. 118600; Last Update:5/26/2004 and Entry No. 600668; Last Edit:3/18/2004 Accessed 10/28/2010.