![]() ![]() When BCKAD is not working, your baby’s body cannot break down the branched chain amino acids. This causes the BCKAD group not to work correctly. If your baby has MSUD, then his or her body is lacking one or more of the enzymes in the BCKAD complex. These three amino acids all share a similar branched shape. You may hear these called the branched-chain amino acids. In maple syrup urine disease (MSUD), the group of enzymes called branched-chain ketoacid dehydrogenase (BCKAD) complex is not working correctly.īCKAD is a group of four enzymes that work together to break down the amino acids leucine, isoleucine, and valine for energy. Other enzymes break down the amino acids. Some enzymes break down proteins into their building blocks, called amino acids. When we eat food, enzymes help break it down. High amounts of branch-chained amino acids in the blood and ketones in the urine might indicate that your baby has MSUD. Certain acids and toxins build up in the body when a child has an amino acid condition, so measuring the amounts of these substances in your baby’s body can help doctors determine if your baby has a condition. Because the harmful effects of untreated MSUD can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.įollow-up testing will involve checking your baby’s urine and blood samples for harmful amounts of acids and toxins. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. If your baby’s newborn screening result for maple syrup urine disease (MSUD) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment. Furthermore, blocking translation of dbt resulted in phenotypes that were similar to those of que mutants ( Friedrich et al., 2012).Your baby’s doctor may ask you if your baby is showing any of the signs of MSUD (see Early Signs, below). The relevance of this protein defect is supported by findings that truncations of the DBT protein at a similar amino acid position in humans result in severe MSUD ( Herring et al., 1992 Friedrich et al., 2012). Reverse transcriptase (RT)-PCR showed that que mutants have abnormal splicing of the dbt gene, causing inclusion of the entire sixth intron, which contains several stop codons, thereby resulting in truncation of the protein by 224 amino acids ( Friedrich et al., 2012). The mutation proved to be a single nucleotide substitution (G to A) in a splice donor site. dbt is predicted to be 493 amino acids and is ∼78% identical to its human counterpart. Using genomic databases and by sequencing nearby genes, the identity of que was found to be dihydrolipoamide branched-chain transacylase E2 ( dbt), which encodes a component of the BCKD complex. To further elucidate the genomic location, single nucleotide polymorphism (SNP) markers were used to determine a specific 0.36 cM interval. First, using positional cloning, it was found that que is located on chromosome 22. Research was then performed to uncover the genetic defect in que mutants. MSUD has an autosomal recessive inheritance pattern and affects approximately one in 185,000 people worldwide, with certain communities having a higher incidence of the disease ( Skvorak, 2009). The CNS is disrupted by the elevated levels of BCAAs and α-keto acids, resulting in dysmyelination, cerebral edema, dystonia, coma, retardation, psychiatric problems and even death within weeks of birth ( Friedrich et al., 2012). The abnormal odor of secretions is among the milder symptoms of the disease. Eliminating the proper function of the BCKD complex results in an accumulation of α-keto acids and BCAAs in plasma and tissues ( Friedrich et al., 2012), resulting in MSUD, which is named after the odor of bodily secretions of those affected by this disease. The BCKD complex responsible for this reaction is composed of three catalytic subunits encoded by four genes ( Friedrich et al., 2012). Next, α-keto acids undergo oxidative decarboxylation through the actions of the mitochondrial branched-chain α-keto acid dehydrogenase (BCKD) complex. The amino acids leucine, isoleucine and valine are first converted to α-keto acids through a transamination reaction. Maple syrup urine disease (MSUD) is a rare inherited central nervous system (CNS) disorder involving defects in the metabolism of branched-chain amino acids. ![]()
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