Blood inherited disorders

There are also RMs which are prepared for a specific application and are used for validation of relevant methods. Cobbaert et al. (1999) made use of Ion Selective Electrode (ISE)-protein-based materials when evaluating a procedure which used an electrode with an enzyme-linked biosensor to determine glucose and lactate in blood. Chance et al. (1999) are involved with the diagnosis of inherited disorders in newborn children and they prepared a series of reference materials consisting of blood spotted onto filter paper and dried, from which amino-acids can be eluted and... 

Phenylketonuria (PKU) is a group of inherited disorders caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH) that catalyses the conversion of phenylalanine to tyrosine, the first step in the pathway for catabolism of this amino acid. As a result, the concentration of phenylalanine in the liver and the blood increases. This high concentration in the liver increases the rate of a side reaction in which phenylalanine is converted to phe-nylpyruvic acid and phenylethylamine, which accumulate in the blood and are excreted in the urine. 

In the early 1980s, the development of HIV/AIDS in young blood transfusion patients was a powerful incentive to find other sources for the blood-derived proteins used to treat hemophilia, a group of inherited disorders affecting the clotting of blood. Hemophilia has... 

In the past decade, eight inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway after the finding of abnormally increased levels of intermediate metabolites in tissues and/or body fluids of patients (Table 5.1.1) [7, 9, 10]. Two of these disorders are due to a defect of the enzyme mevalonate kinase, and in principle affect the synthesis of all isoprenoids (Fig. 5.1.1) [5]. The hallmark of these two disorders is the accumulation of mevalonic acid in body fluids and tissues, which can be detected by organic acid analysis, or preferably, by stable-isotope dilution gas chromatography (GC)-mass spectrometry (GC-MS) [2]. Confirmative diagnostic possibilities include direct measurement of mevalonate kinase activities in white blood cells or primary skin fibroblasts [3] from patients, and/or molecular analysis of the MVK gene [8]. 

This is an inherited disorder in which individuals have a lack of functional LDL receptors preventing cholesterol from being taken up by the tissues. The resulting high blood cholesterol level leads to an increase in the formation of atheromas and can cause death from myocardial infarction during childhood. 

Of the many disorders of lipoprotein metabolism (Tables 5.2 and 5.3), familial hypercholesterolaemia type II may be the most prevalent in the general population. It is an autosomal dominant disorder that results from mutations affecting the structure and function of the ceU-surface receptor that binds plasma LDLs and removes them from the circulation. The defects in LDL-receptor interaction result in lifelong elevation of LDL cholesterol in the blood. The resultant hypercholesterolaemia leads to premature coronary artery disease and atherosclerotic plaque formation. Familial hypercholesterolaemia was the first inherited disorder recognised as being a cause of myocardial infarction (heart attack). 

Diabetes mellitus (DM) is a metabolic carbohydrate disorder that results from either insufficient insulin (type 1 DM) or the body s inability to recognize available insulin (type 2 DM). DM is a multifactorially inherited disorder this means that although people can inherit a propensity toward this condition, environment and diet can trigger onset of the actual disease. People who suffer from DM experience abnormally high blood... 

Pascoe L, Curnow KM. Genetic recombination as a cause of inherited disorders of aldosterone and cortisol biosynthesis and a contributor to genetic variation in blood pressure. Steroids 1995 60 22-7. 

Thiamine deficiency causes decreased pyruvate oxidation, leading to accumulation of pyruvate and lactate, particularly in the blood and brain, and is accompanied by impairment of the cardiovascular, nervous, and gastrointestinal systems (Chapter 38). Inherited deficiency of pyruvate dehydrogenase complex is accompanied by lactic acidemia and abnormalities of the nervous system (e.g., ataxia and psychomotor retardation). Pyruvate carboxylase deficiency causes similar abnormalities (Chapter 15). Both inherited disorders of pyruvate utilization are autosomal recessive. 

Problem Phenylacetic acid (C6H5CH2COOH, simplified here to HPAc) builds up in the blood of persons with phenylketonuria, an inherited disorder that, if untreated, causes mental retardation and death. A study of the acid shows that the pH of 0.12 A/ HPAc is 2.62. What is the of phenylacetic acid ... 

In future work, we wiU extend and validate the different models to other class of diseases. Approximately 1-1.5 % of the French population suffer from dementia and the causes of dementia are neurological disorders such as Alzheimer s disease (which causes 50 %-70 % of aU dementia), blood flow-related (vascular) disorders such as multi-infarct diseases, inherited disorders such as Huntington s disease, and infections such as HIV [15]. In fact, we would like to simulate the patient s progress in order to forecast and to analyze the need for long, medium and short-term care. This allows us to evaluate human, financial and physical resources in the future. 

Phenylacetic acid (CgH5CH2COOH) is one of the substances that accumulates in the blood of people with phenylketonuria, an inherited disorder that can cause mental retardation or even death. A 0.085 M solution of C6H5CH2COOH has a pH of 2.68. Calculate the K value for this acid. 

The porphyrin family of compounds are cyclic tetra-pyrolles many of which are intermediates of the heme biosynthetic pathway. The majority of the compounds of interest to the clinical chemist are not in fact porphyrins (with the exception of protoporphyrin) but porphyrinogens in which all four methylene bridges are in the reduced form. The significance of the porphyrins in medicine relates to the class of inherited disorders - the porphyrias -where there is accumulation of the precursors due to an enzyme deficiency in the heme pathway. The clinical presentation of the porphyrias varies from a chronic photosensitivity to severe acute abdominal pain as in acute intermittent porphyria, which may be precipitated by exposure to certain drugs. Characterization of the type of porphyria depends upon the identification of particular patterns of porphyrins in blood, urine, and feces. 

NBS and the use of dried blood spot (DBS) began almost 50 years ago, when, in the early 1960s, Dr. Robert Guthrie developed a bacterial inhibition assay [1] for the measurement of phenylalanine (Phe). This biological assay utilized cultured bacteria that could only grow in the presence of Phe. This analysis was sufficiently sensitive to measure elevated concentrations of Phe from the DBS of newborns in the first 2-3 days of life. Although a somewhat imprecise assay, it was sufficiently accurate to reliably detect PKU, an inherited disorder of Phe metabolism. Untreated PKU results in profound mental retardation and possible institutionalization. Early and continued treatment by dietary intervention throughout life prevents mental retardation and substantially improves the health of affected individuals. 

In reality, gout is an inherited disorder of metabolism in which uric acid in excessive amounts appears in blood and tissues and produces a painful swelling of the joints of the hands or feet, especially the big toe. 

PKU is an inherited disorder of amino acid metabohsm, with an incidence of 1 in 11000 Uve births in the UK, and thus is relatively common. It is caused by a deficiency of the enzyme phenylhydroxylase, which is the first step of phenylalanine degradation (and also the route for synthesis of tyrosine, melanin, dopamine, etc). If unrecognized, and untreated, the absence of the enzyme phenylalanine in the blood, which in turn causes damage to the developing brain in babies and young children. Clinical features of untreated PKU indue mental retardation, seizures, hyperactivity, and hypopigmentation of the eyes and hair. 

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