Deficiency genetic factors

An idiosyncratic reaction is a harmful, sometimes fatal reaction, that occurs in a small minority of individuals. The reaction may occur with low doses of drags. Genetic factors may be responsible, e.g. glucose-6-phosphate dehydrogenase deficiency, although the cause is often poorly understood. 

Hemophilia A Is Due to a Genetically Determined Deficiency of Factor Vlll... 

Individuals who display a deficiency of factor IX develop haemophilia B, also known as Christmas disease. Although its clinical consequences are very similar to that of a deficiency of factor VIII, its general incidence in the population is far lower. Persons suffering from haemophilia B are treated by i.v. administration of a concentrate of factor IX. This was traditionally obtained by fractionation of human blood. Recombinant factor IX is now also produced in genetically engineered CHO cells (Table 12.2 and Box 12.1). 

There are examples where several genetic factors, including the acetylator phenotype, operate together. Hydralazine toxicity is one such example, which is discussed in detail in chapter 7. Another is the hemolytic anemia caused by the drug thiozalsulfone (Promizole), which occurs particularly in those individuals who are both glucose-6-phosphate dehydrogenase deficient and slow acetylators. Promizole is acetylated, and studies in rapid and slow acetylator mice confirmed that acetylation was a factor as well as an extent of hydroxylation. The latter may also be another factor in humans as is discussed below. 

The causes of human copper deficiency include (1) low intake - malnutrition, total parenteral nutrition (TPN) (2) high loss - cystic fibrosis, nephrotic syndromes and (3) genetic factors — Menkes disease. Copper deficiency may also be associated with chronic malabsorption, a situation which is made much worse in cases of gastric and bowel resection. Several special diets, including powdered milk, liquid protein and standard hospital diets are a means of inducing copper deficiency. The amount of copper in US food has decreased steadily since 1942, and may be related to the rising incidence of coronary artery disease. A copper deficiency may also occur as the result of the use of chelators for other purposes for example, diethyl dithiocarbamate is an in vivo metabolite of ANTABUSE (disulfiram). 

The observation of a chronic urticaria in two sisters who excreted abnormal amounts of xanthurenic acid after a 10-g DL-tryptophan load indicated to Knapp et al. (K6) that constitutional genetic factors may be involved in vitamin Bg-deficiency symptoms. This was borne out by a very high xanthurenic acid level during a similar test on another family. 

Management of the haemophilia A and haemophilia B (genetic deficiencies of factor VIII or IX) is a matter for those with special expertise but the following points are of general interest. 

In rural sub-Saharan Africa, there is a kind of beer which is traditionally brewed in iron vats. The daily iron overload can amount to as much as 200 mg with markedly increased iron absorption (T.H. Bothwell et at, 1965). Such a condition is also observed in South Africa among the black population. Their diet consists of porridge fermented in iron pots with an acid pH value (V.R. Gordeuk et al., 1986). In both conditions, absorption of iron is facilitated by various factors, e. g. protein or vitamin C deficiency, alcohol abuse, acidic diet. It has been suggested that such iron overload is triggered by genetic factors. (437)... 

Genetically, determined clotting diseases include classical haemophilia, which is due to lack of factor VIII, and there is another form of haemophilia due to deficiency of factor IX (Christmas factor). These are treated by giving fresh donor blood or plasma, preparations of factor VIII or factor IX, or increasingly as one of the recombinant versions which are becoming available. 

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