Isolated arterial calcifications of the lower extremities: A clue for NT5E mutation

Abstract

A forty-two year old man was referred to the Dept. of Vascular Medicine because of severe intermittent claudication of both legs, that started at the age of 27. He never smoked, used alcohol in moderation and didn't use illicit drugs. His medication included acetylsalicylic acid and rosuvastatin. His family history was unremarkable, notably with no atherosclerotic disease and no consanguinity. His medical history revealed pain in several small joints of the hands, knees, and ankles since 1994, without rheumatological diagnosis. Physical examination showed absent pulsations of the dorsal pedal arteries on both feet. Laboratory examination revealed normal serum concentration of total cholesterol (3.2 mmol/l), creatinine (71 μmol/l), glucose (5.3 mmol/l), calcium (2.41 mmol/l), inorganic phosphate (0.99 mmol/l), parathyroid hormone (4.3 pmol/l), and 25-OH-vitamin D (56 μmol/l). A CT angiography of the thorax and abdomen was performed in 2007 revealing extensive arterial lower limb calcifications starting from the femoral artery (Fig. 1). Remarkably, the aorta and coronary

<i>NT5E</i> Genetic Mutation Is a Rare But Important Cause of Intermittent Claudication and Chronic Limb-Threatening Ischemia

“…However, the genotype-phenotype relationship is still unknown because only a few cases have been reported. [6][7][8][9][10] Because the disease is late-onset, other factors might also contribute to the severity and timing of onset. Based on the allele frequency, there might be undiagnosed patients with the homozygous variant of NT5E.…”

“…6 Since they unveiled mutations of the NT5E (5′-ectonucleotidase) gene as a cause of CALJA, 6 14 patients from 7 families have been reported around worldwide (Table). [7][8][9][10] Heavily calcified occluded arteries of the lower extremities caused intermittent claudication (IC) as an ischemic symptom in many of these patients, but there is no literature on CALJA patients needing vascular reconstruction for limb salvage. Herein, we report 2 families with identical genetic mutation patterns, and 3 patients needed distal bypass surgeries, including 1 patient with chronic limb-threatening ischemia (CLTI) who had already lost her lower extremity before being diagnosed with CALJA.…”

“…Of the 8 variants of NT5E reported in CALJA patients, 5 are frameshift, splice junction or nonsense mutations, which may disrupt the production of intact protein. [6][7][8][9][10] The disease is thought to be caused by the loss of enzyme…”

Challenging arterial calcification disease associated with rareNT5Egene mutation

“…1 From this first description, only four other families have been described worldwide. [2][3][4][5] In vitro assays demonstrated that CD73deficient fibroblasts reduced extracellular adenosine levels and enhanced the activity of tissue non-specific alkaline phosphatase, which generates procalcifying extracellular Pi. CALJA is an adult-onset disease, with the first symptoms occurring during the second decade of life.…”

NT5E mutation in sisters who underwent aortic valve replacements for aortic stenosis

“…1 Since then, only 14 patients from 7 families have been reported as having CALJA. [2][3][4][5] Patients with CALJA often experience ischemic symptoms in the lower extremities secondary to severely calcified and occluded arteries. CD73 is also known to play a protective role against aortic valve calcification by hydrolyzation of adenosine monophosphate (AMP) to adenosine.…”