Madhavi Ramnath
Genetics and Genomics
Maple Syrup Urine Disease
Maple syrup urine disease (MSUD), first characterized by John Menkes in 1954, is an inborn error of metabolism involving the catabolic pathway of the branched‐chain amino acids, where there is difficulty in breaking down certain parts of the protein (leucine, isoleucine, and valine). This leads to a buildup of chemicals in the blood and the build up of ketoacids, which give rise to the ‘maple syrup’ or burnt sugar smell in the urine of the people with this condition.
Maple syrup disease is an autosomal recessive disorder which means it can be caused by mutation in at least three genes. These genes encode the components of the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex, which catalyses the catabolism of the branched-chain amino acids (BCAAs), leucine, isoleucine and valine. Accumulation of these three amino acids and the buildup of ketoacids leads to encephalopathy and progressive neurodegeneration in an affected …show more content…
Lebo et al. (2000) stated that “Both purported parents were tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed parentage and revealed that a de novo mutation prior to maternal meiosis I, followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two copies of the de novo (an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell) mutant allele.” Therefore during the fertilization by a sperm that did not carry a paternal chromosome 1, the child inherited two mutant MSUD2 alleles on two maternal number 1 chromosomes instead. If both parents carry the MSUD gene, each of their children has a 1 in 4 chance of getting the disorder, and a 1 in 2 chance of being a
Genetics and Genomics
Maple Syrup Urine Disease
Maple syrup urine disease (MSUD), first characterized by John Menkes in 1954, is an inborn error of metabolism involving the catabolic pathway of the branched‐chain amino acids, where there is difficulty in breaking down certain parts of the protein (leucine, isoleucine, and valine). This leads to a buildup of chemicals in the blood and the build up of ketoacids, which give rise to the ‘maple syrup’ or burnt sugar smell in the urine of the people with this condition.
Maple syrup disease is an autosomal recessive disorder which means it can be caused by mutation in at least three genes. These genes encode the components of the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex, which catalyses the catabolism of the branched-chain amino acids (BCAAs), leucine, isoleucine and valine. Accumulation of these three amino acids and the buildup of ketoacids leads to encephalopathy and progressive neurodegeneration in an affected …show more content…
Lebo et al. (2000) stated that “Both purported parents were tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed parentage and revealed that a de novo mutation prior to maternal meiosis I, followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two copies of the de novo (an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell) mutant allele.” Therefore during the fertilization by a sperm that did not carry a paternal chromosome 1, the child inherited two mutant MSUD2 alleles on two maternal number 1 chromosomes instead. If both parents carry the MSUD gene, each of their children has a 1 in 4 chance of getting the disorder, and a 1 in 2 chance of being a