Ectopic calcifications

Hough, T. A., Bogani, D., Cheeseman, M. T., Favor, J., Nesbit, M. A., Thakker R. V., Lyon, M. F. 2004. Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification. Proc. Natl. Acad. Sci. U. S. A. 101(37) 13566-71. 

Collett GD and Canfield AE (2005). Angiogenesis and peric3 tes in the initiation of ectopic calcification. Circ Res 96 930-938. 

The hypercalcemia resulting from hypervitaminosis D is responsible for toxic symptoms such as muscle weakness, bone pain, anorexia, ectopic calcification, hypertension, and cardiac arrhythmias. Toxicity in infants can result in mental and physical retardation, renal failure, and death. 

Serum calcium times phosphorous should not exceed 70 mg/dl to avoid ectopic calcification... 

Adverse effects include headache, weakness, nausea, vomiting, dry mouth, muscle pain, constipation, somnolence, ectopic calcification, hypertension, nephrocalcinosis and weight loss. 

Giving intravenous phosphate is probably the fastest and surest way to reduce serum calcium, but it is a hazardous procedure if not done properly. Intravenous phosphate should be used only after other methods of treatment (bisphosphonates, calcitonin, and saline diuresis) have failed to control symptomatic hypercalcemia. Phosphate must be given slowly (50 mmol or 1.5 g elemental phosphorus over 6-8 hours) and the patient switched to oral phosphate (1-2 g/d elemental phosphorus, as one of the salts indicated below) as soon as symptoms of hypercalcemia have cleared. The risks of intravenous phosphate therapy include sudden hypocalcemia, ectopic calcification, acute renal failure, and... 

Calcium Multiple physiologic actions through regulation of multiple enzymatic pathways Strontium suppresses bone resorption and increases bone formation, calcium and phosphate required for bone mineralization Osteoporosis, osteomalacia, deficiencies in calcium or phosphate Ectopic calcification... 

Fig. 5.1.2 Cholesterol biosynthesis branch of the isoprenoid biosynthetic pathway. Enzymes are numbered as follows 1 squalene synthase 2 squalene epoxidase 3 2,3-oxidosqua-lene sterol cyclase 4 sterol A24-reductase (desmosterolosis) 5 sterol C-14 demethylase 6 sterol A14-reductase (hydrops-ectopic calcification-moth-eaten, HEM, dysplasia) 7 sterol C-4 demethylase complex (including a 3/ -hydroxysteroid dehydrogenase defective in congenital hemidyspla-sia with ichthyosiform nevus and limb defects, CHILD, syndrome) 8 sterol A8-A7 isomerase (Conradi-Hunermann syndrome CDPX2) 9 sterol A5-desaturase (lathosterolosis) 10 sterol A7-reductase (Smith-Lemli-Opitz syndrome). Enzyme deficiencies are indicated by solid bars across the arrows...

Table 5.1.1 Inherited disorders of isoprenoid/cholesterol biosynthesis. CDPX2 Conradi-Hunermann syndrome, CHILD congenital hemidysplasia with ichthyosiform nevus and limb defects, HEM hydrops-ectopic calcification-moth-eaten, MA/HIDS mevalonic aciduria/ hyperimmunoglobulinemia D and periodic fever syndrome, MIM Mendelian Inheritance in Man... 

As an alternative, primary skin fibroblasts or lymphoblasts of patients suspected to be affected with a cholesterol biosynthesis defect can be cultured for 3-7 days in medium supplemented with fetal calf serum depleted of lipoproteins to induce cholesterol biosynthesis, whereupon the specific defect can be determined by sterol analysis using GC-MS as described above. This procedure will readily identify patients affected with Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, hydrops-ectopic calcification-motheaten (HEM) skeletal dysplasia and most patients with Conradi-Hunermann syndrome (CDPX2). Patients with congenital hemidys-plasia with ichthyosiform nevus and limb defects (CHILD) syndrome may not be identified with this assay, but they can be readily diagnosed on the basis of their typical clinical presentation. 

Symptoms of overdose are due mainly to excessive rise in plasma calcium. General effects include malaise, drowsiness, nausea, abdominal pain, thirst, constipation and loss of appetite. Other long-term effects include ectopic calcification almost anywhere in the body, renal damage and an increased calcium output in the urine renal calculi may be formed. It is dangerous to exceed 10 000 units daily of vitamin D in an adult for more than about 12 weeks. 

The prevalence and etiology of ectopic calcification due to alfacalcidol and associated susceptibility factors have been examined in 60 patients with systemic lupus erythematosus (13). The prevalence of ectopic calcification was 40%. Localization of calcification was in peripheral arteries (6.7%), in periarticular areas (33%), and in other soft tissues (17%). The incidence of lupus nephritis and nephrotic syndrome were significantly higher in those with ectopic calcification. Total protein concentrations (70 g/1) in patients with ectopic calcification were significantly lower than in patients without calcification (75 g/1). 

Significantly more of the patient with ectopic calcification had received alfacalcidol (63 versus 19%). The authors concluded that alfacalcidol therapy and lupus nephritis increase the risk of ectopic calcification in patients with systemic lupus erythematosus. 

Ttunoral calcinosis. Tliis is characterized by ectopic calcification around the joints. 

Ectopic calcifications in the blood vessels, brain, subcutaneous tissue, muscles, and cartilage (calcium phosphate is an insoluble salt) (see Figure 75). 

The ectopic calcification in the basal ganglia and in the subcutaneous tissues that is occasionally found in patients with hypo- or pseudohypoparathyroidism is difficult to explain. And it is not known why cataracts develop in both hypo- and pseudohypoparathyroidism. Mental retardation is sometimes described in patients with hypoparathyroidism, but its etiology remains unknown. 

Giachelli, C.M. (1999) Ectopic calcification gathering hard facts about soft tissue mineralization. 

Giachelfi, CM. (2001) Ectopic calcification new concepts in cellular regulation. Zeitschrijijur Kardiologie, 90(SuppL 3), 31 7. 

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