|IMAGES IN RHEUMATOLOGY
|Ahead of print publication
A case of arterial calcification due to deficiency of CD73
Reeta James1, Binoy J Paul1, CK Vasu2
1 Department of General Medicine, KMCT Medical College, Calicut, Kerala, India
2 Department of Radiodiagnosis, KMCT Medical College, Calicut, Kerala, India
|Date of Submission||19-Aug-2020|
|Date of Acceptance||26-Sep-2020|
Department of General Medicine, KMCT Medical College, Manassery, Kozhikode - 673 602, Kerala
Source of Support: None, Conflict of Interest: None
Keywords: Arterial Calcification, CD73, NT5E gene
We report the case of a 43-year-old male born out of nonconsanguineous marriage who presented with recurrent pain and swelling of the small joints of both hands and pain in both knees. On examination, there was tenderness of the proximal interphalangeal joints (PIPJs), distal interphalangeal (IP) joints, and wrist with palpable Heberden's nodes in both hands [Figure 1]a. Pedigree analysis showed that no other family member was affected. Laboratory investigations revealed normal blood counts with erythrocyte sedimentation rate of 30 mm/1st h. Rheumatoid factor and anti-cyclic citrullinated peptide were negative. Serum alkaline phosphatase was within normal limits. Serum calcium level was 9.8 mg/dL and serum phosphorus level was 4.01 mg/dL.
|Figure 1: (a) Hands of the patient showing swelling of the interphalangeal joints and Heberden's nodes. (b) X-ray of the hands (antero-posterior view) showing periarticular calcification and osteoarthritic changes|
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X-ray (antero-posterior [AP] view) of the right hand [Figure 1]b showed capsular and periarticular calcification at the PIPJ of the middle finger, calcification of the 2nd metacarpophalangeal (MCP) joint and first IP joint, calcification of the ulnar collateral ligament, and osteoarthritis-like changes in these joints. X-ray (AP view) of the left hand [Figure 1]b showed capsular and periarticular calcification of the 2nd and 3rd PIPJs and base of the 1st MCP joint, calcific foci in the radiocarpal joint, and calcification of the ulnar collateral ligament with advanced osteoarthritis of these joints. X-ray of the knee [Figure 2] showed extensive calcification of the popliteal artery. There were no signs of distal ischemia, and all peripheral pulses were equally palpable. Arterial and venous Doppler study of both lower limbs showed normal flow.
|Figure 2: X-ray of the knee (antero-posterior and lateral view) showing extensive calcification of the popliteal artery|
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The radiological picture along with arterial calcification and clinical presentation seemed to be highly suggestive of arterial calcification due to deficiency of CD73 (ACDC). Genetic analysis of the patient by clinical exome sequencing revealed homozygous mutation, c1465_1477 del (p. Met4891lefsTer3) on exon 8 of NT5E gene, thereby confirming the diagnosis of ACDC. Genetic analysis of his siblings could not be done due to financial constraints and his parents were no more. Our patient was initiated on 70 mg of alendronate weekly and is on follow-up.
ACDC is a rare autosomal recessive genetic disorder caused by mutation in the NT5E gene, which results in extensive calcification of vessels below the diaphragm, notably the large lower extremity arteries and small joint capsules of the hands and feet. Also known as “calcification of joints and arteries” (CALJA) syndrome, the late-onset profound calcification spares arteries in the trunk and the coronary circulation. Only seven cases of CALJA were reported till 2011, when St Hilaire et al. identified disease-causing NT5E gene mutations in three families with CALJA. Thereafter, about 13 cases have been reported from six families. NT5E gene encodes for CD73, a membrane-bound ecto 5'-nucleotidase, responsible for extracellular Adenosine Triphosphate (ATP) metabolism throughout the body. Adenosine monophosphate (AMP) and pyrophosphate are formed from ATP by the action of ectonucleotide pyrophosphatase-phosphodiesterase 1. Normally, CD73 binds to AMP and converts it to adenosine and inorganic phosphate. Tissue nonspecific alkaline phosphatase (TNAP) is responsible for the breakdown of pyrophosphate throughout the body. Calcification process depends on the levels of pyrophosphate, which is crucial for the inhibition of calcification. TNAP is inhibited by adenosine. NT5E mutation results in little or no functional CD73, ultimately resulting in excessive calcification. The predilection for lower extremity arteries is attributed to the pattern of distribution of adenosine receptors. Intermittent arthritis resembling basic calcium phosphate crystal deposition disease and early-onset osteoarthritis are found to be characteristics of ACDC. Bisphosphonates maybe beneficial in patients with CD73 deficiency, as they are pyrophosphate analogs and hence can inhibit tissue calcification.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]