|55 Kenosia Avenue
Danbury, CT 06810
Toll Free: 1.800.999.6673
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
Copyright 1986, 1988, 1989, 1995, 2003
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.
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.
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.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
PO Box 8126
Gaithersburg, MD 20898-8126
Phone #: 301-251-4925
800 #: 888-205-2311
Home page: http://rarediseases.info.nih.gov/GARD/
1275 Mamaroneck Avenue
White Plains, NY 10605
Phone #: 914-997-4488
800 #: 888-663-4637
Home page: http://www.marchofdimes.com
One AMS Circle
Bethesda, MD 20892-3675 USA
Phone #: 301-495-4484
800 #: 877-226-4267
Home page: http://www.niams.nih.gov/
O'Duffy, JD. Familial Articular Chondrocalcinosis. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:169-170.
Smyth CJ, Holers VM, eds. Gout, hyerucemia and crystal-associated arthropathies. New York: Marcel Dekker, 1999.
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.
Ritter J, et al. ACTH revisited: effective treatment for acute crystal induced synovitis in patients with multiple medical problems. J Rheumatol 1994;21(4):696-99.
Pritzker KP. Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. Curr Opin Rheumatol 1994;6(4):442-47.
Beutler A, et al. Gout and "pseudogout". When are arthritic symptoms caused by crystal deposition? Postgrad Med 1994;95(2):103-106, 109, 113-16.
Ryan LM. Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. Curr Opin Rheumatol 1993;5(4):517-21.
Doherty M, et al. Pyrophosphate arthropathy: a prospective study. Rheumatol 1993;32(3):189-96.
Fam AG. Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. Curr Opin Rheumatol 1992;4(4):574-82.
Abramson SB. Treatment of gout and crystal arthropathies and uses and mechanisms of action of nonsteroidal anti-inflammatory drugs. Curr Opin Rheumatol 1992;4(3):295-300.
McCarthy DJ, Kohn NN, Faires JS. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients. Ann Intern Med 1962;56:711-737.
FROM THE INTERNET
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.
Report last updated: 2008/05/11 00:00:00 GMT+0