Evidence of a Generalized Metabolic Defect in Patients with Hereditary Chondrocalcinosis

Abstract

A gene in the heterozygous state appears responsible for a 2‐fold increase in pyrophosphate content of both fibroblasts and lymphoblasts cultured from patients who have dominantly inherited chondrocalcinosis. Cells from unaffected family members of this large kindred showed a pyrophosphate content in the same range as was found in unaffected, unrelated controls. Similar cells from individuals homozygous for the gene would be useful in delineating the precise biochemical abnormality responsible for the increased pyrophosphate content.

Calcium Pyrophosphate Deposition Disease

“…Lymphocytes and skin fibroblasts from patients with familial CPPD disease show high levels of inorganic pyrophosphate, 42 which suggests a systemic disorder. Recently, Abhishek et al found that patients with nonfamilial chondrocalcinosis had lower cortical bone mineral density and higher rates of vascular and soft-tissue calcification than those without chondrocalcinosis.…”

Familial and clinical aspects of calcium pyrophosphate deposition diseas

“…The possibility of increased pyrophosphate synthesis as the leading mechanism of CPDD crystal deposition is supported by studies from the Milwaukee group [51]. In several in vitro preparations, as well as in studies in patients with sporadic CPPDD and osteoarthritis, evidence has been reported of an increased activity of chondrocyte nucleoside triphosphate pyrophosphohydrolase (NTP-PPH) [51].…”

“…Cervical and lumbar laminectomy have been done in those with spinal stenosis due to calcium pyrophosphate deposition [67,70,71]. Probenecid decreases pyrophosphate synthesis [51,76], whereas phosphocitrate inhibits both the synthesis and mitogenic effects of pyrophosphate [50,83,84]. These may prove useful in the future; however, clinical studies are still not available.…”

“…The exact mechanisms responsible for the deposition of CPPDD crystals remain unknown, although important new information about those mechanisms that mediate calcium-containing crystals induced chronic inflammation and cartilage degeneration is available [50,51].…”

Refinement of the Chromosome 5p Locus for Familial Calcium Pyrophosphate Dihydrate Deposition Disease

“…The activity of this enzyme was elevated in sporadic cases of CPPDD; however, elevated levels of NTPPPH activity were not observed in the familial form of the disease (Ryan et al 1986). Nonetheless, increased levels of inorganic pyrophosphate have been observed in cultured fibroblasts and lymphoblasts of patients affected with familial CPPDD (Lust et al 1981a(Lust et al , 1981b, which thus perpetuates the suspicion that abnormalities in pyrophosphate metabolism may give rise to abnormal crystal deposition in these families.…”