C Deficiency

The deficiency disease described as scurvy has been known for a very long time. There are even records which date back to the time of the Crusades (see the accounts by De Joinville, in 1250, of the disease which beset the crusading armies of Louis IX before Cairo, published in Menard s 1617 edition of De Joinville s writings see also Angelenus, 1604 Kra-mer,2i2 1720 Walter,1748 Lind, 1753 Linton i 1858 Smart, 1888). All these authors described macroscopic changes in tissues and failure of wounds and fractures to heal in scurvy. The first comprehensive account of tissue changes in scurvy were given by Hess in 1920. 

Aschoff and Koch and Hess stressed the fact that the characteristic 

Walter, A Voyage round the World, John and Paul Knapton, London, 1748. 

Linton, Medical and Surgical History of the British Army in the Crimea, 

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In this period, the empirical healing of certain diseases by foods was estabUshed. Examples (3) were the treatment of night blindness (vitamin A deficiency) with hver ia many cultures over centuries, of beriberi (vitamin deficiency) by use of unpoHshed rice by the Japanese navy, of scurvy (vitamin C deficiency) by citms fmits ia the British navy or piae needle extracts by North American natives, and pellagra (niacia deficiency) by a dietary shift away from corn-based foods ia many countries. Other, nondietary empirical treatments iavolved, eg, exposure of children ia northern latitudes to sunlight to cute tickets (vitamin D deficiency) (4). 

Ascorbic acid is very soluble in water and mainly excreted in the urine. No ascorbic acid is excreted during vitamin C deficiency. A minimum amount is lost in the feces, even after intake of gram dosages (154). 

Scurvy results from a dietary vitamin C deficiency and involves the inability to form collagen fibrils properly. This is the result of reduced activity of prolyl hydroxylase, which is vitamin C-dependent, as previously noted. Scurvy leads to lesions in the skin and blood vessels, and, in its advanced stages, it can lead to grotesque disfiguration and eventual death. Although rare in the modern world, it was a disease well known to sea-faring explorers in earlier times who did not appreciate the importance of fresh fruits and vegetables in the diet. 

In addition to the hazards of weather, participants in early polar expeditions often suffered from scurvy, caused by a dietary vitamin C deficiency. 

Coumarin is also widely used for long-term anticoagulation in chronic atrial fibrillation (particularly to avoid cardioembolic strokes), to prevent DVT or PE in patients with chronic hypercoagulability (e.g., congenital AT or protein C deficiency), or to prevent... 

Silk fibroin and collagen illustrate the close linkage of protein stmcture and biologic function. Diseases of collagen mamration include Ehlers-Danlos syndrome and the vitamin C deficiency disease scurvy. 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

Signs of vitamin C deficiency in scurvy include skin changes, fragifity of blood capillaries, gum decay, tooth loss, and bone fracmre, many of which can be attributed to deficient collagen synthesis. 

Tests for hypercoagulable states, such as protein C deficiency and antiphospholipid antibody, should be done only when the cause of stroke cannot be determined based on the presence of well-known risk factors for stroke. 

Homozygous protein C deficiency can cause life-threatening thrombotic syndromes immediately after birth. 

Individuals with heterozygous protein C deficiency are seven times more likely to be afflicted with venous thrombosis than normal individuals. A combination of protein C deficiency with a mutation in the factor V gene (factor V Leiden) carries a much greater risk for venous thrombosis than the presence of only one of these conditions (89). 

Reitsma P. H. Protein C deficiency From gene defects to disease. Thromb Haemost 1997 78, 344-50. 

This of course goes a long way to explaining the association of scurvy with vitamin C deficiency, and the successful utilization by the British navy of lime juice as a means of prevention of the disease - hence the expression limey for British sailors. 

The main value of ACU measurement is that it makes it possible to give a fast estimate of vitamin C deficiency because in healthy subjects ascorbic acid is about 90% of total ACU [33], A strong deficit of ACU, possibly due to vitamin C deficiency, was found in patients with breast tumors (Fig. 11). 

If one reads an account of the outbreak of scurvy on shipboard in the days of long voyages on sailing vessels, he finds indications of individual differences in vitamin C need. For example, in Dana s Two Years before the Mast, one member of the crew was described as suffering from severe scurvy and was about to die of the disease, while many of the crew were quite free from any symptoms. Since they had been living for the same length of time on vitamin C-deficient diets, they would, if uniformly constituted, have all been attacked at about the same time. 

With respect to human beings there is some question as to what level of tissue saturation should ideally be maintained. In guinea pigs defects in developing incisors appear when the tissue concentrations are about 40 per cent of the maximum. Scurvy symptoms do not appear until the tissue saturation has reached a much lower level (about 20 per cent saturation). It seems logical to suppose that in different individuals the manifestations of mild vitamin C deficiency would be different and that a high degree of saturation would be safest from the standpoint of all the vulnerable tissues. 19... 

In view of the probable differences in the vulnerability of different tissues in different individuals, it may well be that the vitamin C needs for best health could vary from individual to individual more than the amount of vitamin C necessary for tissue saturation. It may easily be the case, for example, that some individuals are healthy and free from minor symptoms when their tissues are 50 per cent saturated Others, because of the greater vulnerability of specific tissues may require that their tissues be highly saturated at all times. Dalldorf 49 hints at something like resistant vitamin C deficiency when he says, "Even these large amounts [75 to 100 mg. daily], however, are inadequate to maintain saturation in certain patients" (italics added). He cites that in Hodgkins disease, protracted fever from various causes, active rheumatic heart disease, and tuberculosis, the vitamin C requirement may be "extremely high."... 

Williams, R.S., 2000, Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell 101 389-399. 

Selected prolines and lysines are hydroxylated by prolyl and lysyl hydroxylases. These enzymes, located in the RER, require ascorbate (vitamin C), deficiency of which produces scurvy. 

Vitamin K deficienqr should be distinguished from vitamin C deficiency. Table 1-10-3 sumitia-rizes some of these differences. 

Answer E. The patient has many signs of scurvy from a vitamin C deficiency. The diet, which contains no fruits or vegetables, provides little vitamin C, Prolyl hydroxylase requires vitamin C, and in the absence of hydroxylation, the collagen a-chains do not form stable, mature collagen. The anemia may be due to poor iron absorption in the absence of ascorbate. 

The formation of Hyp and Hyl residues in procollagen is catalyzed by iron-containing oxygenases ( proline and lysine hydroxylase, EC 1.14.11.1/2). Ascorbate is required to maintain their function. Most of the symptoms of the vitamin C deficiency disease scurvy (see p. 368) are explained by disturbed collagen biosynthesis. 

Protein C concentrate (Human) Purpura fuhninans and coumarin-induced skin necrosis in patients with severe congenital protein C deficiency... 

The deficiency state scurvy is characterized by degenerative changes in the capillaries, bone, and connective tissues. Mild vitamin C deficiency symptoms may include faulty bone and tooth development, gingivitis, bleeding gums, and loosened teeth. 

Patients with CHF may exhibit greater than expected PT/INR response to warfarin. Protein C deficiency Known or suspected hereditary, familial, or clinical deficiency in protein C has been associated with necrosis following warfarin therapy. 

Vitamin C deficiency leads to impaired collagen production and defective collagen structure,... 

The answer is B. The patient shows many signs of vitamin G deficiency or scurvy, which is seen most frequently in infants, the elderly, and in alcoholic patients. Particularly indicative of vitamin C deficiency are the multiple small hemorrhages that occur under the skin (petechiae) and nails and surrounding hair follicles. Bleeding gums are a classic indicator of scurvy. 

Coumarin-induced skin necrosis is a rare complication of oral anticoagulant therapy. Especially patients suffering from a rare and life-threatening blood disorder known as protein C deficiency are at risk. In these cases Protein C Concentrate (human). 

Ceprotin, can be given. Ceprotin is of course also indicated for patients with severe congenital Protein C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. 

Deficiency may occur in infants if no fruits or vegetables are added to their milk formulas. In alcoholics, and in elderly subjects who consume inadequate diets vitamin C deficiencies are frequent. Severe ascorbic acid deficiency is characterized by the syndrome known as scurvy. Its manifestations are generally based on a loss of collagen. Symptoms include hemorrhages, loosening of teeth. In children cellular changes in the long bones occur. 

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