Chondrocalcinosis 2

Alternative Names

  • CCAL2
  • Chondrocalcinosis, Familial Articular
  • Calcium Gout
  • Calcium Pyrophosphate Arthropathy
  • Calcium Pyrophosphate Dihydrate Deposition Disease
  • CPPDD
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WHO-ICD-10 version:2010

Diseases of the musculoskeletal system and connective tissue

Arthropathies

OMIM Number

118600

Mode of Inheritance

Autosomal dominant

Gene Map Locus

5p15.2

Description

Chondrocalcinosis 2 (CCAL2) is a chronic articular disorder described by acute intermittent attacks of arthritis and the presence of calcium hypophosphate crystals in synovial fluid, cartilage, and periarticular soft tissue (lining of soft tissue with calcium). CCAL2 symptoms include osteoarthritis, joint pain, and stiff joints, these symptoms occur due to the deposit of crystals containing calcium, which causes pain, inflammation, and weakens the cartilage of the joints causing it to break easily. CCAL2 occurs in three forms: sporadic form (idiopathic), hereditary form, and a form correlated with metabolic diseases like hyperparathyroidism, hypothyroidism, Wilson disease, and hemochromatosis. The sporadic form occurs in middle-aged or elderly subjects, meanwhile hereditary form and forms associated with other disease occur at an earlier age.

CCAL2 male to female ratio is about 1.4:1. CCAL2 is treated based on the degree of involvement such as patients demonstrating common presentation like arthritic symptoms will pursue the treatment allocated to osteoarthritis (OA) which includes physical therapy, adapted activity, and non-steroidal anti-inflammatory drugs (NSAIDS). If these treatments prove to be ineffective, surgical interference is suggested. Meanwhile, subjects experiencing acute attacks involving pain and disability will undergo arthrocentesis mixed with management of an intra-articular steroid. Moreover, patients experiencing re-current episodes are provided with NSAIDS and colchicines for further prevention. Recent research demonstrated the effective role of ethylene diamine tetra acetic acid (EDTA) for the treatment of CCAL2, however, due to the significant adverse effects EDTA is still under massive examination.

Chondrocalcinosis 2 (CCAL2) occurs due to mutations in the ANKH gene. ANKH protein consists of 492 amino acids, with a molecular weight of 54,241 kD, and includes a multi-pass transmembrane domain. The protein is expressed in the joints, bones and further tissues, and it controls pyrophosphate levels in cultured cells. Research suggested that certain  polymorphisms in the ANKH gene might be correlated with the normal differentiation in bone size and shape amongst persons, leading to the alteration of ANKH gene activity which influences the pyrophosphate levels within the extracellular matrix.

Epidemiology in the Arab World

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Other Reports

Kuwait

A study was carried out by Malaviya et al. (2001) to determine the prevalence of chondrocalcinosis within adult Arabs suffering from knee arthritis and to conduct an observational study of calcium pyrophosphatase dehydrate crystal deposition disease (CPPD-CDD) among Arabs in Kuwait. A prospective radiological survey was employed on the knee joints of 100 consecutive subjects (70 males and 30 females aged 45-80 years) throughout 1997 to determine the prevalence of chondrocalcinosis. Meanwhile, the observational study of CPPD-CDD went over a period of five years (1994-1999) and included polarized light microscopy to determine the occurrence of crystals in synovial fluid and oil-oil immersion microscopy to increase the sensitivity of the lightly centrifuged samples. The cohort of 100 patients consisted of 82 Kuwaitis and 18 patients of Middle-Eastern Arab origin, of those two male Kuwaiti subjects aged 50 and 75 years, respectively, were found to suffer from chondrocalcinosis in the knee. Reporting the younger age of the studied group demonstrated a figure that was similar to those found in research performed in Western countries. The five year study comprised a cohort of 2,726 new patients demonstrating crystal arthritis in 85 subjects (3%), out of the 85 patients, 14 subjects were found to suffer from definite (eight cases) or probable (six cases) CPPD-CDD. Patients demonstrated several clinical presentations including acute monarthritis (pseudogout), premature generalized osteoarthritis, and polyarticular rheumatoid-like presentations. Malaviya et al. (2001) concluded that CPPD-CDD may not be rare amongst Arabs in the Gulf region and proposed employing the analysis of crystals throughout joints aspirates examination for the aim of considering it as a differential diagnosis in the future.

Qatar

At Hamad General Hospital in Qatar, Hammoudeh and Siam (1998) reported a 24 year old female with pseudogout. Despite the follow-up that lasted over a decade, the patient was found not to possess any family history of the disease and did not experience any associated diseases.

Tunisia

Hamza et al. (1992) carried out a clinical and radiological survey on 77 members of a Tunisian family suffering from familial chondrocalcinosis with incomplete penetrance. An X-ray of seven living members of three generations revealed articular chondrocalcinosis that emerged early throughout their lives leading to broad radiological engagement. The employment of electron microscopy on biopsies of synovium and cartilage of single patient revealed calcium pyrophosphate dehydrogenase crystals, meanwhile HLA typing demonstrated that all affected patients carried the haplotype A1 B12 DR3.

Bejia et al. (2004) conducted a family study following the observation of a 35-year-old patient who developed CPPDD. Physical examination and radiograph analysis in 103 family members older than 18 years revealed 15 members to have CPPDD. There were 10 men and five women, with a mean age of 59.4 years. Onset was usually in the third or fourth decade. The disease was mild. Yet, four clinical patterns were found: Five patients had pseudogout, five had pseudoosteoarthritis, three had asymptomatic disease, and two had pseudorheumatoid arthritis. Inheritance was autosomal dominant with low penetrance and with no associations with specific HLA antigens.

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