A Deficiency Diseases

The normal requirement of vitamin A for adults is supplied by an adequate diet. The rational uses of retinol are in the treatment of vitamin A deficiency and as prophylaxis in high-risk subjects during periods of increased requirement, such as infancy, pregnancy, and lactation. Once vitamin A deficiency has been diagnosed, intensive therapy should be instituted. The patient should then be maintained on a proper diet. 

There are many types of preparations that contain retinol. Absorption is greatest for aqueous preparations, intermediate for emulsions, and slowest for oil solutions. Whereas oil-soluble preparations may lead to greater hepatic storage of the vitamin, water-miscible preparations usually provide higher concentrations in plasma. Vitamin A is available as capsules. Tretinoin (all-trans-retinoic acid Retin A) is available for topical use. Isotretinoin (13-ri.s-retinoic acid Accutane) is available for oral use, as is etretinate (Tegison). 

During pregnancy and lactation, it is advisable to increase the maternal intake of vitamin A by about 25%. As the typical North American diet readily provides adequate intake of the vitamin, supplementation is not routinely indicated. 

In kwashiorkor and other severe vitamin A deficiencies in children, a single intramuscular injection of 30 mg of retinol as the water-miscible palmitate has been advocated, followed by intermittent oral treatment with retinoids. 

Vitamin A may be helpful in certain diseases of the skin, such as acne, psoriasis, Darier s disease, and ichthyosis. 

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The term vitamin is a misnomer, the name means vital amines, and while vitamins are essential for life they are not, as was originally supposed, amines. Most vitamins were discovered as a result of a deficiency disease produced by a restricted diet. Long voyages on sailing ships with a diet composed of ship s biscuit, dried beans, dried peas and salted meat produced scurvy. In the worst cases the whole crew were affected, but the ship s officers tended to be less severely affected. 

P2a. Peck, S. M., Chargin, L., and Sobotka, H., Keratosis follicularis (Darier s disease). A vitamin A deficiency disease. Arch. Dermatol, and Syphilol. 43, 223-229 (1941). 

Studies on the History of Rickets. I. Recognition of Rickets as a Deficiency Disease. Pharmacy in History, 16, 83-88 (1974)... 

The principal physiological functions of tins vitamin include growth, production of visual purple, maintenance of skin and epithelial cells, resistance to infection, gluconeogenesis. mucopolysaccharide synthesis, bone development, maintenance of myelin and membranes, maintenance of color and peripheral vision, maintenance of adrenal cortex and steroid hormone synthesis, Specific vitamin A deficiency diseases include xerophthalmia, nyctalopia, hemeralopia, keratomalacia, and hyperkeratosis. 

Ascorbic acid is a vitamin in primates. In most other animals, it can be synthesized by a branch of the glucoronic acid pathway (Chapter 18). It is apparently not changed into any coenzyme in the human being and participates as a vitamin in a reducing capacity in several biochemical reactions. These include the post-translational hydroxylation of proline in collagen biosynthesis (Chapter 8) and in tyrosine metabolism (Chapter 20). Ascorbic acid is oxidized to dehydroascorbic acid, a diketo derivative of ascorbate. Scurvy is a deficiency disease caused by a shortage of dietary ascorbic acid. In children, this results in defective bone formation in adults, extensive bleeding occurs in a number of locations. Scurvy is to be suspected if serum ascorbic acid levels fall below 1 jug/mL. 

Nutrient deficiency diseases occur when there is an absence of nutrients which are essential for growth and health. Lack of food leading to either malnutrition or starvation gives rise to these diseases. Another cause for a deficiency disease may be due to a structural or biological imbalance in the individual s metabolic system. 

The amounts of most nutrients, especially vitamins, needed to both prevent and treat deficiency diseases are small. The average intake of Img of vitamin Bi is sufficient to prevent a deficiency disease of that vitamin, while lOmg of B could cure an advanced case of someone about to die of beriberi. Although small doses of vitamins cure deficiencies, large doses of some vitamins such as A and D can be harmful since these two vitamins are already stored by the liver. Vitamins A and D are fat soluble vitamins and can accumulate to the point of becoming toxic. Most other vitamins are water soluble and are excreted in the urine throughout the day. 

W3. Wills, L., Studies in pernicious anaemia of pregnancy tropical macrocytic anaemia as a deficiency disease with special reference to the vitamin B complex. Indian J. Med. Res. 21, 669-681 (1934). 

Osteomalacia is a deficiency disease. Insufficient vitamin D leads to low plasma calcium levels. This stimulates the secretion of PTH, which causes release of calcium from bone and failure to mineralize new bone. Characteristic bone deformities result in children and bone pain and tenderness in affected adults. Treatment is by vitamin D replacement. 

Even at this late stage the list of mistaken causes of scurvy was being added to. McCollum, in 1917 proposed that scurvy was not a deficiency disease at all, but was due to constipation, which resulted in bacterial infection through the walls of the caecum, produced by the nature of the diet. 

We now know that scurvy is a deficiency disease and it must have existed throughout all history. However, it was really the very long sea journeys of the early Middle Ages which drew attention to it, though any disasters which affected the food supply, such as sieges, would also result in an upsurge of scurvy. It would appear, however, that we can identify at least three major factors which contributed to the failure to recognise the cure for scurvy. 

It all works much better if we consider some simpler cases that are less obvious in ordinary life but still have greater importance for medicine than skin or eye color. Take, for example, the disease phenylketonuria, which 1 mentioned briefly in Chapter 8. If left untreated it produces severe mental retardation and, in many cases, death before the age of 25. It is caused by an incapacity to convert the aminoacid phenylalanine into another aminoacid, tyrosine. It is not, however, a deficiency disease, because its harmful effects are not caused by a shortage of tyrosine, and cannot be avoided by adding tyrosine to the diet. Instead they are caused by the toxic effects on the brain of a substance called phenylpyruvate, which the body produces in its efforts to remove the excess of phenylalanine. The name of the disease reflects the fact that phenylpyravate, which belongs to a general class of chemical substances known as phenylketones, is excreted in the urine of affected people. This provides a simple method of diagnosis, and the disease is treated by carefully controlling the diet so that it provides no more phenylalanine than is needed for normal health. There is then no surplus to be converted into phenylpyruvate. 

Deficiency of vitamin A leads to degenerative lesions in the epithelium, xerophthalmia being the classical vitamin A deficiency disease. The drug-equivalent uses of vitamin A can be seen in Table 1. 

The foregoing arguments suggest the possibility that under certain circumstances a deficiency disease may be localized in the human body in such a way that only some of the manifestations usually associated with the disease are present. Let us consider, for example, a vitamin or other vital substance that is normally metabolized by the... 

Water is a vital constituent of all cells and a regular intake is essential to maintain life. Small quantitiesof a range of chemicals known as vitamins are also needed for healthy existence. The absence of a vitamin leads to a deficiency disease such as scurvy which occurs when vitamin C is absent from the diet. It is available in fresh vegetables, oranges and lemons. Vitamin D is formed by the action of ultraviolet light on a chemical in the skin (7-dehydrocholesterol), and is present in milk and cod liver oil. Absence of this vitamin may lead to rickets. 

Somewhat later, the Dutch physician Cornelius Elders remarked on the similarity of pernicious anemia and the tropical sprue he had seen in Java. Sprue, he said, is a deficiency disease, and If [the two] have the same aetiology it is most probable that pernicious anaemia, like sprue, is a deficiency disease, and as such should be curable, or at least amenable to improvement by well-chosen food. Ruminating on these facts, Castle asked himself ... 

Dam H, Schonheyder F. A deficiency disease in chicks resembling scnrvy, Biochem J 1934 28 1355-1359. 

Indifference lack of interest or concern. A type of behavior sometimes found in a deficiency disease. 

Fig B-25 Beriberi, a deficiency disease due to a lack of vitamin B-1 (thiamin) in the diet. Note the cracked skin and swollen l s (edema). In the Far East, beriberi is largely due to the almost exclusive use of polished rice. (Courtesy, FAO, Rome, Italy.)... 

EATING PATTERNS WHICH LEAD TO DIETARY DEFICIENCIES. Although hunger due to a lack of a sufficient quantity of food often causes a deficiency disease(s), the factors which lead to this problem are discussed elsewhere. (See HUNGER, WORLD MALNUTRITION, PROTEIN-ENERGY POPULATION, WORLD and WORLD POOD.) Herein, the dietary patterns which may cause deficiency diseases even though sufficient quantity of food is available are identified as follows ... 

The mystery of beriberi, an ancient disease among rice- eating peoples in the East, was eventually unraveled as a deficiency disease caused by a lack of thiamin. 

In 1747, James Lind, an English naval surgeon, tested six remedies on 12 sailors who had scurvy and found that oranges and lemons were curative. His classical studies, the results of which were published in 1753, are generally credited as being the first experiments to show that an essential food element can prevent a deficiency disease. But another 50 years elapsed before the British Navy required rations of lemons or limes on sailing vessels. 

Denis Burkitt and Neil Painter then began what they might not— but I certainly do—regard as modern substantiation for the old concept of health foods, in their article Diverticular Disease of the Colon—a deficiency disease of Western Civilisation. ... 

Vitamin E was discovered as the antisterility factor of the female rat. Deficiency in experimental animals results mainly in atrophy of the testes and dystrophy of muscles. In man, a deficiency disease is not knoiMi some authors, however, suspect that muscular dystrophy may be connected with vitamin E deficiency. 

The name ascorbic acid derives from scurvy, a deficiency disease much feared by mariners through the ages and curable by ascorbic acid. The principal manifestations are capillary lesions, hemorrhages, gingivitis, and loosening of the teeth. Man s requirement for the vitamin exceeds that of other vitamins by one or two orders of magnitude. The reason for this is obscure. 

A vitamin is a complex oiganic substance required in the diet in small amounts, whose absence leads to a deficiency disease. Nine vitamins are water soluble (B group and C). They are normally stored in very small amounts and therefore are needed on a regular basis. They are generally not toxic in excess. The B group of vitamins acts as cofactors in the pathways of intermediary metaboUsm. 

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