Diseases, dystrophies

DNA sequence data have been used to investigate inherited diseases such as hemophilia and muscular dystrophy, and also in cancer research. 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

In 1956 selenium was identified (123) as an essential micronutrient iu nutrition. In conjunction with vitamin E, selenium is effective iu the prevention of muscular dystrophy iu animals. Sodium selenite is adrninistered to prevent exudative diathesis iu chicks, a condition iu which fluid leaks out of the tissues white muscle disease iu sheep and infertility iu ewes (see Eeed ADDITIVES). Selenium lessens the iacidence of pneumonia iu lambs and of premature, weak, and stillborn calves controls hepatosis dietetica iu pigs and decreases muscular inflammation iu horses. White muscle disease, widespread iu sheep and cattle of the selenium-deficient areas of New Zealand and the United States, is insignificant iu high selenium soil areas. The supplementation of animal feeds with selenium was approved by the U.S. EDA iu 1974 (see Eeed additives). Much of selenium s metaboHc activity results from its involvement iu the selenoproteia enzyme, glutathione peroxidase. 

Worton, R., 1995. Mnscnlar dystrophies Diseases of die dystrophin-glycoprotein complex. Science 270 755-756. 

The only one of these conditions which causes progressive and degenerative disease of muscle is myotonic dystrophy. Inheritance is autosomal dominant, but expression is very variable. The condition also illustrates the phenomenon of... 

The histopathological features of muscle samples from patients with myotonic dystrophy are not particularly distinctive. Early changes appear to be a selective atrophy of type 1 fibers, and hypertrophy of type 2 fibers, but the biochemical and/or physiological basis of these possibly related phenomena is not known. The incidence of degenerating fibers increases with age, although the presence of internally nucleated muscle fibers in early stages of the disease suggests that the muscle retains... 

There is no single underlying cause for the myotonia seen in the muscles of myotonic patients. The typical myotonic response is a train of action potentials generated in a muscle fiber in response to a single stimulus. Experimental work has shown that such a response can be generated in normal muscle fibers in which chloride conductance is suppressed, and this may be the cause of the myotonia of Thomsen s disease (see Barchi, 1988 for examples). It is almost certainly not the cause of myotonia in myotonic dystrophy in which there is an associated fall in... 

Karpati, G., Ascadi, G. (1993). The potential for gene therapy in Ducheiuie muscular dystrophy and other genetic muscle diseases. Muscle Nerve 16, 1141-1153. 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

Scriver CR et al (editors) The Metabolic and Molecular Bases of Inherited Disease, 8th ed. McGraw-Hill, 2001. (This comprehensive four-volume text contains coverage of malignant hyperthermia [Chapter 9], channelopathies [Chapter 204], hypertrophic cardiomyopathy [Chapter 213]> the muscular dystrophies [Chapter 216], and disorders of intermediate filaments and their associated proteins [Chapter 221].)... 

Nineteen women underwent amniocentesis for the determination of fetal sex. Several different X-llnked abnormalities constituted the Indications for this procedure, and these Included hemophilia A, hemophilia B, Duchenne muscular dystrophy, optic albinism, X-llnked mental retardation, the Lesch-Nyhan syndrome (due to dlflclency of hypoxanthlne-guanlne phosphorlbosyltransferase, and Fabry s disease (due to deficiency of an a-galact-osldase). Fourteen of the fetuses were male. Including one which turned out to be a set of twins, and most of the male pregnancies were terminated. The sex determination being carried out for Fabry s disease Is of particular Interest, since In this case It was desired to find out whether the fetus was a female. 

Poly(L-lysine) has also been suggested as a carrier for pepstatin, a specific inhibitor of the lysosomal proteinase cathepsin D, responsible for causing muscle-wasting diseases, such as muscular dystrophy [257],... 

RFLPs are often a reflection of individual genetic diversity and are not related to a clinical phenotype, but occasionally they can be diagnostic of an inherited disease. This technique is relatively new yet, it has been applied to the prenatal detection of sickle cell anemia, thalassemia, phenylketonuria, a,-antitrypsin deficiency, Huntington s chorea, Duchenne muscular dystrophy, hemophilia A and B, cystic fibrosis, and several other, diseases. 

Reverse genetics has been applied to diseases such as Duchenne muscular dystrophy and cystic fibrosis, in which the responsible enzymes are unknown and the disease results from a significant deletion. By combining RFLP analysis with cytogenetics, it has been possible to increasingly narrow the location of the defective genes to small regions on the affected chromosomes. 

Enteric Myopathies. The familial types include the dominant type 1 [150], the recessive type 2 with ophthalmoplegia [151] and the recessive type 3 [116]. The sporadic types include muscular dystrophies [152] including myotonic dystrophy [153] and Duchenne s dystrophy. Dysmotility has been associated with all these diseases. 

Human creatine kinase -MM MAK33 IgGl Cardiac disease, mitochondrial disorders, inflammatory myopathies, myasthenia, polymyositis, McArdle s disease, NMJ disorders, muscular dystrophy, ALS, hypo and hyperthyroid disorders, central core disease, acid maltase deficiency, myoglobinuria, rhabdomyolysis, motor neuron diseases, A. thaliana A. thaliana 2S2 seed storage protein SP + 0.02-0.4% TSP of fresh leaf extract (10-12% TSP of intercellular fluid) 52... 

Other leukodystrophies are associated with the lysosomal and peroxisomal disorders in which specific lipids or other substances accumulate due to a deficiency in a catabolic enzyme - for example Krabbe s disease, meta-chromatic leukodystrophy (MLD) and adrenoleuko-dystrophy (ALD) [1,2]. (These are discussed in detail in Ch. 40.) Similarly, disorders of amino acid metabolism can lead to hypomyelination - for example phenylketonuria and Canavan s disease (spongy degeneration) [1, 2, 25] (Ch. 40). The composition of myelin in the genetically... 

Duchenne and Becker muscular dystrophies (DMD and BMD) are X-linked, allelic, neuromuscular diseases. DMD/BMD are characterized by progressive muscular weakness and degeneration of skeletal muscle. DMD is the most common recessive lethal disease, with an incidence of approximately 1 in 3500 newborns, and according to estimates, one-third of the cases are linked with new mutations (M3). Clinical symptoms of the disease appear earlier, by 2 to 3 years of age, in the form of retarded motor development. Progressive symptomatic children show weakness and wasting of muscle and are usually wheelchair bound approximately by the age of 11-12 years. It has been reported that most patients die at about the age of 20 due to pneumonia, which is related to chronic respiratory insufficiency. BMD—being the rarer allelic disorder—has a milder clinical course with slower disease progression. The BMD-affected patients usually survive beyond the age of 30. 

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