ppt课件-maplesyrupurinedisease-auburnuniversity.pptVIP

Maple Syrup Urine Disease MSUD Maple Syrup Urine Disease is a genetic disease in which the amino acids leucine, isoleucine and valine cannot be broken down by branched-chain alpha-keto acid dehydrogenase. /overv.htm General Information Introns: 8 Size of mRNA: 1781 bp Size of Protein: 445 aa Location: 19q13.1-13.2 Domains: 4 /Structure/cdd/wrpsb.cgi Domains E1_dh, Dehydrogenase E1 component Transketolase_N, Transketolase AcoA, Pyruvate/2-oxoglutarate dehydrogenase complex TktA, Transketolase Genes and Protein 4 Genes that could be possibly mutated: BCKDHA * BCKDHB DBT DLD Protein affected: branched-chain alpha-keto acid dehydrogenase (BCKD) Structure /Structure/mmdb/mmdbsrv.cgi?db=tform=6dopt=suid=12936 Types of MSUD Classical: little or no enzyme activity 2% Intermediate: more enzyme activity 3-8% Can tolerate greater amount of leucine Intermittent: even more enzyme activity 8-15% Thiamine-responsive: thiamine to increase enzyme activity /overv.htm Mutations 4 mutations in the BCKDHA gene that can result in MSUD Classic: Tyrosine to Asparagine at aa 394 Classic: 8bp deletion from nucleotide 887-894 Intermediate: Glycine to Arginine at aa 245 Intermediate: Phenylalanine to Cysteine at aa 364 /entrez/dispomim.cgi?id=608348 Results of Mutations in BCKDHA Cannot breakdown amino acids leucine, isoleucine, and valine Build up to toxic levels Nervous system degeneration Can lead to encephalopathy About MSUD Recessive genetic disease – meaning that both parents must carry a mutation for the disease. Each person has two genes that code for enzyme activity. If only one gene is mutated, then the person is just a carrier of MSUD. If parents are both carriers, 1 in 4 chance that baby has MSUD 2 in 4 chance that baby will be carrier 1 in 4 chance that baby will not have mutation Characteristic Symptoms Symptoms occur in newborns within the first four to seven days of birth. Infants with this disease have poor feeding habits. Vomiting Infants show poor weight gain d