Deficiencies, genetic diseases

Biochemistry of Zinc and Copper Zinc in the -Cells of the Pancreas Absorption of Zinc and Copper Plasma Zinc and Copper Levels Metallothionein and Ceruloplasmin Zinc Excretion and Zinc Deficiency Copper Excretion and Copper Deficiency Genetic Diseases of Copper Metabolism Molybdenum, Sulfite, and Sulfate Molybdenum Molybdenum Biochemistry Sulfite Sulfate... 

The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

Scurvy affects the structure of collagen. However, it is due to a deficiency of ascorbic acid (Chapter 45) and is not a genetic disease. Its major signs are bleeding... 

A third autosomal recessive genetic disease is a -antitrypsin deficiency. Abnormalities in the a,-antitrypsin protein impair secretion from the liver, a,-Antitrypsin deficiency causes cirrhosis in children as well as adults adults usually have concomitant pulmonary disease such as chronic obstructive pulmonary disease. 

Certain subgroups of the population may be more susceptible to the toxic effects of lead exposure. These include crawling and house-bound children (<6 years old), pregnant women (and the fetus), the elderly, smokers, alcoholics, and people with genetic diseases affecting heme synthesis, nutritional deficiencies, and neurological or kidney dysfunction. This is not an exhaustive list and reflects only current data available, further research may identify additional susceptible subgroups. 

A much more serious genetic disease, first described by Foiling in 1934, is phenylketonuria. Here the disturbance in phenylalanine metabolism is due to an autosomal recessive deficiency in liver phenylalanine hydroxylase (Jervis, 1954) which normally converts significant amounts of phenylalanine to tyrosine. Phenylalanine can therefore only be metabolized to phenylpyruvate and other derivatives, a route which is inadequate to dispose of all the phenylalanine in the diet. The amino acid and phenylpyruvate therefore accummulate. The condition is characterized by serious mental retardation, for reasons which are unknown. By the early 1950s it was found that if the condition is diagnosed at birth and amounts of phenylalanine in the diet immediately and permamently reduced, mental retardation can be minimized. The defect is shown only in liver and is not detectable in amniotic fluid cells nor in fibroblasts. A very sensitive bacterial assay has therefore been developed for routine screening of phenylalanine levels in body fluids in newborn babies. 

Leptospermone (34), a representative of an important new class of herbicides from the bottlebrush plant, Callistemon citrinus (Curtis) Skeels, has been found to have an inhibitory effect on the enzyme, -hydroxyphenylpyruvate dioxygenase (HPPD), involved in the synthesis of plastoquinone in plants. Nitisinone (35), a synthetic derivative of (34), has recently been introduced to the market for the treatment of hereditary tyrosinemia type 1 (HT-1), a severe genetic disease caused by a deficiency of fumaryl acetoacetate hydrolase (FAH). ... 

C6PD deficiency is the most common genetic disease in the world, affecting over 400 million people, most of whom are men, because the gene Is located on the X chromosome. 

Comment on "Whole blood levels of dodecanoic acid, a routinely detectable forensic marker for a genetic disease often misdiagnosed as sudden infant death syndrome (SIDS) MCAD deficiency". 

Gene therapy holds great promise for the treatment of many diseases (e.g., cancer, AIDS, cystic fibrosis, adenosine deaminase deficiency, cardiovascular diseases, Gaucher disease, a 1-antitrypsin deficiency, rheumatoid arthritis, and several others) (1,2). Advances in genomics and molecular biology have revealed that almost all diseases have a genetic component. In some cases, such as cystic fibrosis or hemophilia,... 

Examples of other important genetic diseases associated with amino acid metabolism Other important genetic diseases associated with amino acid metabolism include albinism, homocystinuria, methylmalonyl CoA mutase deficiency, alkaptonuria, histidinemia, and cystathioninuria. 

Thus, it has been found that genetic diseases run the gamut of time and of severity. In Pompc s disease, a deficient enzyme (alpha-1,4-glucosidasc) may range from death (total deficiency) to the progressive manifestation of cardiac or peripheral myopathy in later life (mild deficiency). 

Thus, knowledge of the structure of the oligosaccharides that accumulate in the urine and tissues of patients suffering from glycopro-teinoses has allowed the definition of the nature of the enzymic deficiencies that are a consequence of grave genetic diseases, and has led... 

Genetic diseases can be divided into two main groups based on whether they are caused by relatively few common mutations or by many unique mutations. Tay-Sachs disease, a fatal neurodegenerative disorder caused by a deficiency of hexosaminidase A, is common in the Ashkenazi Jewish population. Three hexosaminidase mutations account for 96% of the disease in the Ashkenazi Jewish population (9). In contrast most patients with Fabry disease, a metabolic disorder caused by deficiency of the enzyme galactosi-dase A, have unique mutations in the galactosidase A gene (10). This... 

In one sense, the incidence of genetic impairment is 100%. None of us is without some genetic deficiency and all of us will die, mostly from a cause that includes a genetic component. From this viewpoint, it is meaningless to ask the total incidence or the total cost. Can we be more specific We are interested here in the contribution of recurrent mutation to genetic impairment. This implies that we should classify genetic diseases by their mode of inheritance. 

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