Genetic diseases maple syrup urine disease

As discussed above, in the case of phenylketonuria, early intervention can make the difference between mental retardation and a near normal life course for a newborn. Congenital adrenal hyperplasia and maple syrup urine disease are two examples of neonatal hereditary disorders where early diagnosis and medical intervention can make the difference between life and death for the newborn. In addition, in a number of genetic diseases, early diagnosis and treatment can help ameliorate symptoms these include fragile X syndrome, homocystinuria, sickle cell anemia, cystic fibrosis, and many /1-thalassemias. 

Faiibrother WG, Yeh RF, Sharp PA, Bulge CB (2002) Predictive identification of exonic splicing enhancers in human genes. Science 297 1007-1013 Fisher CW, Fisher CR, Chuang JL, Lau KS, Chuang DT et al (1993) Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease multiple-exon skipping as a secondary effect of the mutations. Am J Hum Genet 52 414-424... 

Branched-Chain Oxo-acid Decarboxylase and Maple Syrup Urine Disease The third oxo-add dehydrogenase catalyzes the oxidative decarboxylation of the branched-chain oxo-acids that arise from the transamination of the branched-chain amino acids, leucine, isoleuctne, emd vtdine. It has a similEU subunit composition to pyruvate and 2-oxoglutarate dehydrogenases, and the E3 subunit (dihydrolipoyl dehydrogenase) is the stune protein as in the other two multienzyme complexes. Genetic lack of this enzyme causes maple syrup urine disease, so-called because the bremched-chain oxo-acids that are excreted in the urine have a smell reminiscent of maple syrup. 

Maple syrup urine disease is a genetic disease involving a defect in BCKA dehydrogenase. The disease affects one in 100,000 births, manifests in infants as leth-... 

GlO. Goedde, H. W., and Keller, W., Metabolic pathways in maple syrup urine disease. In "Amino Acid Metabolism and Genetic Variation (W. L. Nyhan, ed.), pp. 191-214. McGraw-HiU, New York, 1967. 

Maple syrup urine disease is a rare genetic disorder affecting the metabohsm of leucine, isoleucine and valine. Accumulation of these branched-chain amino acids results in severe neurological damage and death. The aim of dietary management is to prevent the accumulation of these amino acids, by the use of a low-protein diet and leucine-, isoleucine-and vahne-free amino acid preparations. Natural protein supplies the necessary leucine, isoleucine and valine, based on a leucine exchange system with additional isoleucine and/ or valine available as single amino acid supplements. 

Frazier DM, et al. Nutrition management guideline for maple syrup urine disease tm evidence- and consensus-based approach. Mol Genet Metab. 2014 112(3) 210-7. 

Strauss KA, et al. Classical maple syrup urine disease and brain development principles of management and formula design. Mol Genet Metab. 2010 99(4) 333 5. 

Van Calcar SC, et al. Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. Am J Med Genet. 1992 44(5) 641-6. 

Lombeck I, Kasperek K, Feinendegen LE, Bremer HJ (1978) Trace element disturbances in dietetically treated patients with phenylketonuria and Maple Syrup Urine Disease. Monogr. Hum. Genet. 9 114-117... 

INBORN ERRORS OF THE METABOLISM. At times the metabolism of the nutrients cannot proceed normally due to some defect in the genetic information that exists at birth or shortly thereafter. These defects can affect the metabolism of carbohydrates, proteins, and fats hence, they are referred to as inborn errors of metabolism. Often they are due to production of a nonfunctional enzyme or complete lack of an enzyme involved in the metabolic scheme. Since enzymes are protein, their production relies upon correct genetic information. Many of these inborn errors have serious consequences, but fortunately most are rare. Familiar examples of errors in carbohydrate metabolism include lactose intolerance and galactosemia. Familiar examples of errors in protein metabolism include albinism, maple syrup urine disease, and phenylketonuria. The hyperlipoproteinemias are familiar examples of inborn errors of fat metabolism. 

Rudiger, H.W., Langenbeck, U., Schulze-Schencking, M., Goedde, H.W. and Schuchmann, L. (1972), Defective decarboxylase in branched chain keto acid oxidase multienzyme complex in classical type of Maple Syrup Urine Disease. Hum. Genet., 14, 257. 

T There is a relatively rare genetic disease in which the three branched-chain a-lceto acids (as well as their precursor amino acids, especially leucine) accumulate in the blood and spill over into the urine. This condition, called maple syrup urine disease because of the characteristic odor imparted to the urine by the a-lceto acids, results from a defective branched-chain a-lceto acid dehydrogenase complex. Untreated, the disease results in abnormal development of the brain, mental retardation, and death in early infancy. Treatment entails rigid control of the diet, limiting the intake of valine, isoleucine, and leucine to the minimum required to permit normal growth. ... 

When transaminated, the three branched-chain amino acids (valine, leucine, and isoleucine) form compounds that have the characteristic odor of maple symp. An enzyme known as branched-chain a-keto acid dehydrogenase converts these compounds into CoA esters. People who do not have this enz3me have the genetic disease known as maple syrup urine disease—so-called because their urine smells like maple syrup. 

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