Maple Syrup Urine Disease
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What is maple syrup urine disease?
Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. Beginning in early infancy, this condition is characterized by poor feeding, vomiting, lack of energy (lethargy), seizures, and developmental delay. The urine of affected infants has a distinctive sweet odor, much like burned caramel, that gives the condition its name. Maple syrup urine disease can be life-threatening if untreated.
Maple syrup urine disease can be classified by its pattern of signs and symptoms or by its genetic cause. The most common and most severe form of the disease is the classic type, which appears soon after birth. Variant forms of the disorder appear later in infancy or childhood and are typically milder, but still involve mental and physical retardation if not treated.
How common is maple syrup urine disease?
Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide. The disorder occurs much more frequently in the Old Order Mennonite population, in which the incidence is about 1 in 358 newborns.
What genes are related to maple syrup urine disease?
Mutations in the BCKDHA, BCKDHB, DBT, and DLD genes cause maple syrup urine disease.
These four genes provide instructions for making proteins that work together as a complex. This complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food (particularly protein-rich foods such as milk, meat, and eggs). Mutations in any of these genes reduce or eliminate the function of the complex, preventing the normal breakdown of leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. Because high levels of these substances are toxic to the brain and other organs, their accumulation leads to the serious medical problems associated with maple syrup urine disease.
How do people inherit maple syrup urine disease?
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.
Source: National Institutes of Health
New human genetics research reported from University of Porto
2009 JUL 8 - (NewsRx.com) -- "Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder of branched-chain amino acid metabolism. In the context of the wide mutational spectrum known for this disease, a few common mutations have been described in populations where founder effects played a major role in modeling diversities," scientists writing in the journal Annals of Human Genetics report. "In Portugal, for instance, a high proportion of patients are of Gypsy origin and all share the same mutation (c.117delC-alpha; p.R40GfsX23), causing the neonatal severe form of MSUD. In this study, we used four microsatellite markers closely flanking the BCKDHA gene (E1 alpha protein) to demonstrate that c.117delC-alpha is a founder mutation responsible for the high incidence of the disorder among Portuguese Gypsies. These results are of medical relevance since carrier tests and prenatal diagnosis can be offered to families at risk, particularly because the carrier frequency of c.117delC-alpha was estimated at 1.4% among the healthy Portuguese Gypsies from the South of the country," wrote S. Quental and colleagues, University of Porto. The researchers concluded: "Finally we present evidence that the genomic region of the BCKDHA gene where c.117delC-alpha is located is likely a mutational hotspot, since recurrence of c.117delC-alpha was observed in two distinct population groups.." Quental and colleagues published their study in Annals of Human Genetics (Revisiting MSUD in Portuguese Gypsies: Evidence for a Founder Mutation and for a Mutational Hotspot within the BCKDHA Gene. Annals of Human Genetics, 2009;73(Part 3):298-303). Additional information can be obtained by contacting S. Quental, University of Porto, IPATIMUP, Institute Pathology & Molecular Immunology, Rua Dr. Roberto Frias S-N, P-4200465 Oporto, Portugal. The publisher of the journal Annals of Human Genetics can be contacted at: Wiley-Blackwell Publishing, Inc., Commerce Place, 350 Main St., Malden 02148, MA, USA. Keywords: Portugal, Oporto, Life Sciences, Metabolic Disease, Genetics, Maple Syrup Urine Disease, Metabolism, Human Genetics, University of Porto. This article was prepared by Genetics & Environmental Health Week editors from staff and other reports. Copyright 2009, Genetics & Environmental Health Week via NewsRx.com.
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