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Maple syrup urine disease ( MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine, particularly prior to diagnosis and during times of acute illness.
What is maple syrup urine disease (MSUD)?
Newborn screening for maple syrup urine disease involves analyzing the blood of 1–2 day-old newborns through tandem mass spectrometry. The blood concentration of leucine and isoleucine is measured relative to other amino acids to determine if the newborn has a high level of branched-chain amino acids.
How is maple syrup urine disease diagnosed in newborns?
The disease is named for the presence of sweet-smelling urine, similar to maple syrup, when the person goes into metabolic crisis. Along with the smell being present in ear wax of an affected individual during metabolic crisis.
Why does my urine smell like maple syrup?
Is maple syrup urine disease gene or chromosome mutation?
MSUD is caused by changes (mutations) in one of three different genes: BCKDHA, BCKDHB and DBT. Mutations in these genes result in absent or decreased activity of human branched-chain alpha-ketoacid dehydrogenase complex (BCKAD) enzymes.
What mutation causes maple syrup disease?
Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder. This disorder is usually caused by mutations in any one of the genes; BCKDHA, BCKDHB and DBT, which represent E1α, E1β and E2 subunits of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, respectively.
Who is most likely to get maple syrup urine disease?
MSUD can affect anyone, but people whose parents are closely related are much more likely to have the metabolic disease. For this reason, MSUD frequently occurs among Mennonites in the United States, where members of the community often marry each other. MSUD occurs in 1 of every 380 births in the Mennonite population.
What is the life expectancy of someone with maple syrup urine disease?
If untreated, life-threatening coma or respiratory failure could occur within 7 to 10 days and most will die within several months.
What causes maple syrup disease?
Causes of maple syrup urine disease Maple syrup urine disease is caused by mutations in one of three genes – BCKDHA, BCKDHB or DBT. These genes provide instruction for the human body to make enzymes (BCKDH complex enzymes) which are essential for breaking down amino acids including leucine, isoleucine, and valine.
What is the genetic inheritance pattern of maple syrup urine disease?
Inheritance. This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
What research is being done on maple syrup urine disease?
A study in human skin cells and mice shows the widely-used diabetes drug metformin reduces toxic acid levels in Maple Syrup Urine Disease. The discovery offers the possibility of a new treatment for a disorder identified 1 in 180,000 births.
What is maple syrup disease?
MSUD. Maple syrup urine disease (MSUD) is a disorder in which the body cannot break down certain parts of proteins. The urine of people with this condition can smell like maple syrup.
What is maple syrup urine disease?
Description. Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly.
What genes cause maple syrup?
Mutations in the BCKDHA, BCKDHB, and DBT genes can cause maple syrup urine disease. These three genes provide instructions for making proteins that work together as part of a complex. The protein complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food, ...
Why is maple syrup toxic?
Because high levels of these substances are toxic to the brain and other organs, their accumulation leads to the serious health problems associated with maple syrup urine disease. Researchers are studying other genes related to the same protein complex ...
How many babies are affected by maple syrup?
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, with an estimated incidence of about 1 in 380 newborns.
What is autosomal recessive gene?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where is the genetics home reference?
Genetics Home Reference has merged with MedlinePlus. Genetics Home Reference content now can be found in the "Genetics" section of MedlinePlus. Learn more
Can maple syrup cause coma?
If untreated, maple syrup urine disease can lead to seizures, coma, and death. Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy ...
Why does my urine smell like maple syrup?
The disease is named for the presence of sweet-smelling urine, similar to maple syrup, when the person goes into metabolic crisis. Along with the smell being present in ear wax of an affected individual during metabolic crisis. In populations to whom maple syrup is unfamiliar, the aroma can be likened to fenugreek, and fenugreek ingestion may impart the aroma to urine. Symptoms of MSUD varies between patients and is greatly related to the amount of residual enzyme activity.
How to test for maple syrup in newborns?
Newborn screening for maple syrup urine disease involves analyzing the blood of 1–2 day-old newborns through tandem mass spectrometry. The blood concentration of leucine and isoleucine is measured relative to other amino acids to determine if the newborn has a high level of branched-chain amino acids. Once the newborn is 2–3 days old the blood concentration of branched-chain amino acids like leucine is greater than 1000 μmol/L and alternative screening methods are used. Instead, the newborn's urine is analyzed for levels of branched-chain alpha-hydroxyacids and alpha-ketoacids.
What is the cause of maple syrup odor?
The buildup of these BCAAS will lead to the maple syrup odor that is associated with MSUD. The BCKAD complex begins by breaking down leucine, isoleucine, and valine through the use of branch-chain aminotransferase into their relevant α-ketoacids. The second step involves the conversion of α-ketoacids into acetoacetate, acetyl-CoA, and succinyl-CoA through oxidative decarboxylation of α-ketoacids. The BCKAD complex consists of four subunits designated E 1 α, E 1 β, E 2, and E 3. The E 3 subunit is also a component of pyruvate dehydrogenase complex and oxoglutarate dehydrogenase complex. MSUD can result from mutations in any of the genes that code for these enzyme subunits, E 1 α, E 1 β, E 2, and E 3. Mutations of these enzyme subunits will lead to the BCKAD complex unable to break down leucine, isoleucine, and valine. The levels of these branched chain amino acids will become elevated and lead to the symptoms associated with MSUD. Glutamate levels are maintained in the brain by BCAA metabolism functions and if not properly maintained can lead to neurological problems that are seen in MSUD individuals. High levels of leucine has also been shown to affect water homeostasis within subcortical gray matter leading to cerebral edema, which occurs in MSUD patients if left untreated.
What amino acids build up in MSUD?
Leucine (pictured above), Isoleucine, and valine are the branched-chain amino acids that build up in MSUD. Maple syrup urine disease ( MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia.
What is MSUD in biology?
MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKAD), leading to a buildup of the branched-chain amino acids ( leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine.
How to manage MSUD?
Keeping MSUD under control requires careful monitoring of blood chemistry, both at home and in a hospital setting. DNPH or specialised dipsticks may be used to test the patient's urine for ketones (a sign of metabolic decompensation ), when metabolic stress is likely or suspected. Fingerstick tests are performed regularly and sent to a laboratory to determine blood levels of leucine, isoleucine, and valine. Regular metabolic consultations, including blood-draws for full nutritional analysis, are recommended; especially during puberty and periods of rapid growth. MSUD management also involves a specially tailored metabolic formula, a modified diet, and lifestyle precautions such as avoiding fatigue and infections, as well as consuming regular, sufficient calories in proportion to physical stress and exertion. Without sufficient calories, catabolism of muscle protein will result in metabolic crisis. Those with MSUD must be hospitalised for intravenous infusion of sugars and nasogastric drip-feeding of formula, in the event of metabolic decompensation, or lack of appetite, diarrhea or vomiting. Food avoidance, rejection of formula and picky eating are all common problems with MSUD. Some patients may need to receive all or part of their daily nutrition through a feeding tube.
What are the symptoms of MSUD?
Untreated in older individuals, and during times of metabolic crisis, symptoms of the condition include uncharacteristically inappropriate, extreme or erratic behaviour and moods, hallucinations, lack of appetite, weight loss, anemia, diarrhea, vomiting, dehydration, lethargy, oscillating hypertonia and hypotonia, ataxia, seizures, hypoglycaemia, ketoacidosis, opisthotonus, pancreatitis, rapid neurological decline, and coma. Death from cerebral edema will likely occur if there is no treatment. Additionally, MSUD patients experience an abnormal course of diseases in simple infections that can lead to permanent damage.
What is maple syrup urine disease?
Maple syrup urine disease is an inherited (genetic) condition that prevents the body from processing proteins correctly. Your body breaks down the protein you eat into parts called amino acids. Your body then uses those amino acids to make other proteins that it needs to function.
What causes maple syrup in urine?
Maple syrup urine disease is caused by a change in one of three genes: BCKDHA, BCKDHB, or DBT. These genes give your body instructions for making enzymes that form a complex that helps break down branched-chain amino acids.
How long does it take for maple syrup to show up in urine?
Signs of maple syrup urine disease can vary widely and usually start shortly after birth (1 to 10 days). Symptoms can result from eating foods or milk the body cannot break down or by going long periods without eating. Illness or infection can also bring on symptoms.
How to check for maple syrup in newborn?
Newborn screening for maple syrup urine disease is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
How many chances of having a child with maple syrup?
Parents who already have a child with maple syrup urine disease still have a 1 in 4 chance of having another child with maple syrup urine disease. This 1 in 4 chance stays the same for all future children.
Can a carrier have a child with maple syrup?
Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children. If two parents are carriers of a nonworking copy of the BCKDHA, BCKDHB, or DBT gene, they have a 1 in 4 chance of having a child with maple syrup urine disease.
Is maple syrup a genetic disease?
Maple syrup urine disease is a genetic condition. Babies inherit it from their biological (birth) parents. To learn more about genetic conditions, visit MedlinePlus Genetics.
Overview
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness.
Signs and symptoms
The disease is named for the presence of sweet-smelling urine, similar to maple syrup, when the person goes into metabolic crisis. The smell is also detected in ear wax of an affected individual during metabolic crisis. In populations to whom maple syrup is unfamiliar, the aroma can be likened to fenugreek, and fenugreek ingestion may impart the aroma to urine. Symptoms of MSUD varies between patients and is greatly related to the amount of residual enzyme activity.
Causes
Mutations in the following genes cause maple syrup urine disease:
• BCKDHA (OMIM: 608348)
• BCKDHB (OMIM: 248611)
• DBT (OMIM: 248610)
• DLD (OMIM: 238331)
Pathophysiology
MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKAD), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The buildup of these BCAAS will lead to the maple syrup odor that is associated with MSUD. The BCKAD complex begins by breaking down leucine, isoleucine, and valine through the use of branch-chai…
Diagnosis
Prior to the easy availability of plasma amino acid measurement, diagnosis was commonly made based on suggestive symptoms and odor. Affected individuals are now often identified with characteristic elevations on plasma amino acids which do not have the characteristic odor. The compound responsible for the odor is sotolon (sometimes spelled sotolone).
On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendatio…
Prevention
There are no methods for preventing the manifestation of the pathology of MSUD in infants with two defective copies of the BCKD gene. However, genetic counselors may consult with couples to screen for the disease via DNA testing. DNA testing is also available to identify the disease in an unborn child in the womb.
Treatment
Keeping MSUD under control requires careful monitoring of blood chemistry, both at home and in a hospital setting. DNPH or specialised dipsticks may be used to test the patient's urine for ketones (a sign of metabolic decompensation), when metabolic stress is likely or suspected. Fingerstick tests are performed regularly and sent to a laboratory to determine blood levels of leucine, isoleucine, and valine. Regular metabolic consultations, including blood-draws for full nutritional …
Prognosis
If left untreated, MSUD will lead to death due to central neurological function failure and respiratory failure. Early detection, diet low in branched-chain amino acids, and close monitoring of blood chemistry can lead to a good prognosis with little or no abnormal developments. Average intellectual development is below that of the general population and the severity of the deficit is a related to the time the condition remained undiagnosed and the effectiveness of dietary control i…