Genetic disorders deficiencies

While purine deficiency states are rare in human subjects, there are numerous genetic disorders of purine catabolism. Hyperuricemias may be differentiated based on whether patients excrete normal or excessive quantities of total urates. Some hyperuricemias reflect specific en2yme defects. Others are secondary to diseases such as cancer or psoriasis that enhance tissue turnover. 

Another condition involving ceruloplasmin is aceru-loplasminemia. in this genetic disorder, levels of ceruloplasmin are very low and consequently its ferroxidase activity is markedly deficient. This leads to failure of release of iron from cells, and iron accumulates in certain brain cells, hepatocytes, and pancreatic islet cells. Affected individuals show severe neurologic signs and have diabetes mellitus. Use of a chelating agent or administration of plasma or ceruloplasmin concentrate may be beneficial. 

The other factor deficiencies are rare genetic disorders. Mutations in the gene for the respective clotting factors results in impaired functionality or production of the factor (Table 64-7). 

Up to now, 101 different mutations have been identified (Fig. 11) (B29, H18). Most of the variant enzymes are produced by one or two missense mutations in the structural gene. G6PD Vancouver is caused by three nucleotide substitutions (M4). Although nucleotide deletions or nonsense mutations are common molecular abnormalities that may cause a variety of genetic disorders, they are rare in G6PD deficiency cases. Nucleotide deletions have been found in only five variants... 

Parkinson s disease 253-4, 298 pathophysiology of iron in humans 228 absorption disorders 211-20 acquired and genetic disorders 207 deficiency... 

Pyruvate carboxylase (also called PC) is an enzyme that converts pyruvate to oxaloacetate (shown as oxaloacetic acid in the citric acid cycle diagram). Pyruvate carboxylase deficiency is a genetic disorder that is characterized by insufficient quantities of pyruvate carboxylate in the body. How do you think this disorder affects the citric acid cycle Use print and electronic resources to research pyruvate carboxylase deficiency. Find out what its symptoms are, and how it affects the body at the molecular level. Also find out what percent of the population is affected, and how the deficiency can be relieved. Present your findings as an informative pamphlet. If possible, conduct an e-mail interview with an expert on the disorder. 

Phenylalanine (Phe or F) (2-amino-3-phenyl-propanoic acid) is a neutral, aromatic amino acid with the formula HOOCCH(NH2)CH2C6H5. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and Phe play a significant role not only in protein structure but also as important precursors for thyroid and adrenocortical hormones as well as in the synthesis of neurotransmitters such as dopamine and noradrenaline. The genetic disorder phenylketonuria (PKU) is the inability to metabolize Phe. This is caused by a deficiency of phenylalanine hydroxylase with the result that there is an accumulation of Phe in body fluids. Individuals with this disorder are known as phenylketonurics and must abstain from consumption of Phe. A nonfood source of Phe is the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester), which is metabolized by the body into several by-products including Phe. The side chain of Phe is immune from side reactions, but during catalytic hydrogenations the aromatic ring can be saturated and converted into a hexahydrophenylalanine residue. ... 

It should not be assumed that all birth defects and functional abnormalities in children are caused by drugs or environmental chemicals. It is clear that environmental factors such as extreme heat or cold, certain forms of radiation, infections (particularly German measles and syphilis), dietary deficiencies, and genetic disorders in the parents can all put the developing fetus at risk. 

Although ER protein degradation seems not be essential for yeast cells, the breakdown of mutated and thus malfolded ER proteins is often associated with severe diseases in human (Ciechanover, 1998 Plemper and Wolf, 1999). The importance of this process in the understanding of genetic disorders like cystic fibrosis and a 1-antitrypsin deficiency has been outlined above. In the following we will give further examples on how viruses or toxins may misuse the machinery for the ER protein degradation to interfere with cellular processes. 

Chronic Addison s disease congenital adrenal hyperplasia (genetic disorder due to deficiency of steroidogenic enzymes). 

Rare genetic disorders, including Tangier disease and LCAT (lecithin cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients. Reductase inhibitors and fibric acid derivatives exert lesser effects. 

In the urea cycle, two molecules of ammonia combine with a molecule of carbon dioxide to produce a molecule of urea and water. The overall cycle involves a series of biochemical reactions dependent on enzymes and carrier molecules. During the urea cycle the amino acid ornithine (C5H12N202) is produced, so the urea cycle is also called the ornithine cycle. A number of urea cycle disorders exist. These are genetic disorders that result in deficiencies in enzymes needed in one of the steps in the urea cycle. When a urea cycle deficiency occurs, ammonia cannot be eliminated from the body and death ensues. 

Recessive X-linked ichthyosis (RXLI) is a dermatological condition that is caused by steroid sulfatase deficiency (STSD), although the mechanism by which the deficiency causes the characteristic scaly skin has not been adequately explained. RXLI is the most common genetic disorder of steroid metabolism, affecting about 1 2000 males. Epstein and workers [16] first demonstrated that serum cholesterol sulfate was elevated in the condition, and this compound has become the preferred analyte for diagnosis. The serum level is more than tenfold greater than normal in the condition. 

The study of enzymes has immense practical importance. In some diseases, especially inheritable genetic disorders, there may be a deficiency or even a total absence of one or more enzymes. For other disease conditions, excessive activity of an enzyme may be the cause. Measurements of the activities of enzymes in blood plasma, erythrocytes, or tissue samples are important in diagnosing certain illnesses. Many drugs exert their biological effects through interactions with enzymes. And enzymes are important practical tools,... 

In familial HDL deficiency, HDL levels are very low they are almost undetectable in Tangier disease. Both genetic disorders are the result of mutations in the ABC1 protein. Cholesterol-depleted HDL cannot take up cholesterol from cells that lack ABC1 protein, and... 

Correct answer = B. o1-Antitrypsin deficiency is a genetic disorder that can cause pulmonary emphysema even in the absence of cigarette use. An deficiency of a1-antitrypsin permits increased elastase activity to destroy elastin in the alveolar walls, even in nonsmokers. a1-antitrypsin deficiency should be suspected when chronic obstructive pulmonary disease develops in a patient younger than 45 years who does not have a history of chronic bronchitis or tobacco use, or when multiple family members develop obstructive lung disease at an early age. 

Two genetic disorders of copper metabolism, Wilson s disease (see Section 62.2.3.3) and Menkes disease, are known. The latter involves impaired intestinal absorption of copper56,57 as well as probably subcellular metabolic defects which result in copper deficiency with respect to metal-loenzyme activity. The characteristic steely hair in Menkes disease results from free SH bonds in hair protein because of failure of lysyl oxidase to produce the disulfide links. Depigmentation of hair and skin, hypothermia, cerebral degeneration, central nervous system retardation, skeletal demineralization and arterial degeneration are all seen. Copper supplements may benefit hypothermia and increase pigmentation but the disease is not generally cured. 

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