Cornelia D Cudrici1, Kam A Newman2, Elisa A Ferrante1, Rebecca Huffstutler1, Katherine Carney1, Blas Betancourt2, Markku Miettinen3, Richard Siegel2, James D Katz2, Leon J Nesti4, Cynthia St Hilaire5,6, Deepak Lakshmipathy1, Han Wen1, Mohammad H Bagheri7, Manfred Boehm1, Alessandra Brofferio1. 1. National Heart, Lung, and Blood Institute, Bethesda, MD, USA. 2. National Institutes of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA. 3. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 4. Walter Reed National Military Medical Center, Clinical and Experimental Orthopaedics, Bethesda, MD, USA. 5. Department of Medicine, Division of Cardiology and Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 6. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. 7. Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Abstract
OBJECTIVES: Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5'-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. METHODS: Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. RESULTS: Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. CONCLUSION: This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms. Published by Oxford University Press on behalf of the British Society for Rheumatology 2021.
OBJECTIVES: Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5'-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. METHODS: Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. RESULTS: Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. CONCLUSION: This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms. Published by Oxford University Press on behalf of the British Society for Rheumatology 2021.
Authors: Cynthia St Hilaire; Shira G Ziegler; Thomas C Markello; Alfredo Brusco; Catherine Groden; Fred Gill; Hannah Carlson-Donohoe; Robert J Lederman; Marcus Y Chen; Dan Yang; Michael P Siegenthaler; Carlo Arduino; Cecilia Mancini; Bernard Freudenthal; Horia C Stanescu; Anselm A Zdebik; R Krishna Chaganti; Robert L Nussbaum; Robert Kleta; William A Gahl; Manfred Boehm Journal: N Engl J Med Date: 2011-02-03 Impact factor: 91.245
Authors: Adrian Pendleton; Michelle D Johnson; Anne Hughes; Kyle A Gurley; Andrew M Ho; Michael Doherty; Josh Dixey; Pierre Gillet; Damien Loeuille; Rodney McGrath; Antonio Reginato; Rita Shiang; Gary Wright; Patrick Netter; Charlene Williams; David M Kingsley Journal: Am J Hum Genet Date: 2002-09-20 Impact factor: 11.025