User:Paigeunderwood/sandbox

Miranda Kaster--Classic severe MSUD is the most common of the classifications.  Those born with classic severe MSUD seem normal in the beginning.  At about one week of age the newborn will start to lose weight, appear lethargic and begin showing indication of hypotonia and hypertonia. Following these symptoms are seizures then a coma, and death if no treatment takes place.

Miranda Kaster--Intermediate MSUD is a less severe type of MSUD.  It is caused by the branched amino acids, but it is considered less severe because there are less acute episodes of decompensation.  Patients normally do not show signs of the disorder until 10-12 months old. 

Paige Underwood--

Split up "Management" section into different headings directly onto wikipedia page. (approved)

Diet Control Section- added source to cover information

A diet with carefully controlled levels of the amino acids leucine, isoleucine, and valine must be maintained at all times in order to prevent neurological damage. Since these three amino acids occur in all natural protein, and most natural foods contain some protein, any food intake must be closely monitored, and day-to-day protein intake calculated on a cumulative basis, to ensure individual tolerance levels are not exceeded at any time. As the MSUD diet is so protein-restricted, and adequate protein is a requirement for all humans, tailored metabolic formula containing all the other essential amino acids, as well as any vitamins, minerals, omega-3 fatty acidsand trace elements (which may be lacking due to the limited range of permissible foods), are an essential aspect of MSUD management. These complement the MSUD patient's natural food intake to meet normal nutritional requirements without causing harm.^[10] If adequate calories cannot be obtained from natural food without exceeding protein tolerance, specialised low protein products such as starch-based baking mixtures, imitation rice and pasta may be prescribed, often alongside a protein-free carbohydrate powder added to food and/or drink, and increased at times of metabolic stress. Some patients with MSUD may also improve with administration of high doses of thiamine, a cofactor of the enzyme that causes the condition

1. http://www.sciencedirect.com/science/article/pii/S1096719214001607

Liver Transplantation Section- found source to cover material, moved, added, and removed phrases to make section clear and concise

Usually MSUD patients are monitored by a dietitian. Liver transplantation is another treatment option that can completely and permanently normalise metabolic function, enabling discontinuation of nutritional supplements and strict monitoring of biochemistry and caloric intake, relaxation of MSUD-related lifestyle precautions, and an unrestricted diet. The transplant surgery itself carries standard risks as it requires extensive hospitalisation and rigorous adherence to a tapering regime of medications. Following transplant, the risk of periodic rejection will exist. However, the odds of its success are greatly elevated when the only indication for it is an inborn error of metabolism. Case studies show it is most successful when performed at a young age, or when the patient has proper dietary control of their BCAA. Weaning from immunosuppressants may even be possible in the longrun. With proper management after the transplant, the affected patient is able to live a healthy, normal life without suffering the severe neurological damage associated with the disease. Despite normalising clinical presentation, liver transplantation is not considered a genetic cure for MSUD because the patient will still carry two copies of the mutated BKAD gene, which could be passed on to each of their biological children.

2. http://www.sciencedirect.com/science/article/pii/S1096719214001607

Danielle Koerner-- Signs and Symptoms Section

http://www.omim.org/entry/248600

Added sections for Early Onset MSUD and Later Onset MSUD directly onto wikipedia page (and that was approved)

Added several citations for other symptoms (they were approved and condensed; mostly from OMIM); had to go back and change the citations that included scopes since those were not allowed on the page (since not all people have access to those)

I added: "weight loss, diarrhea, hypertonia, edema, etc" but then also added citations to the remaining symptoms.

I added the following sentences: "Additionally, maple syrup urine disease patients often experience an abnormal course of disease in simple infections that become increasingly severe and can have permanent damage. In more rare cases, concomitant osteoporosis^[5] may also appear in these patients."

I also started the Later Onset MSUD paragraph with the following: "The symptoms of MSUD may also present later depending on the severity of the disease.^[4]" as a transition between the early and late onset.

According to OMIM, there were 4 categories of disease: classic severe, intermediate, intermittent, and thiamine responsive.

Intermittent Maple Syrup Urine Disease:-Michelle Gilden Growing up, children with this form of MSUD will develop normally. They are able to eat a normal diet including normal levels of leucine, unlike classic or intermediate MSUD. Under normal life conditions The lab values for a person with Intermittent MSUD would include normal levels of Urine organic acids, and normal plasma amino acid levels in the blood.They can potentially have a slightly elevated level of Branched chain amino acids such as Leucine, Isoleucine,and Valine. Under abnormal conditions, such as times of physiological stress or bodily infection, the classic signs of MSUD will surface and can potentially be lethal.

Intermittent Maple Syrup Urine Disease: Danielle Koerner- children show symptoms at a variety of ages with this disease. The symptoms appear at a variety of ages and sometimes gradually decrease over time or at a certain point in time. If they symptoms become severe enough before the bought is complete, there is a change the individual will die.

Thiamine-Responsive Maple Syrup urine Disease: - Michelle Gilden Those with Thiamine-Responsive MSUD do not usually show symptoms of this disease in the neonatal period, or even at an early age. This is normally seen later in life and has symptoms similar to Intermediate MSUD. This specific form of MSUD can be maintained with Thiamine supplementation and restriction of branched chain amino acids.

Thiamine-Responsive Maple Syrup Urine Disease: Danielle Koerner- It is important to careful monitor the diet of the patient with this type of Maple Syrup Urine Disease. It is an allosteric site that is affected by this type of disease, not the actual binding site. Thus, the affinity for the ligand is affected but still can bind. Stabilization means that there is a smaller allosterically inhibiting effect.

Epidemiology--Michelle Gilden

Maple Syrup Urine Disease affects 1 in 185,000 births in the United States. It is rare in this population, but it is very prominent in Old Order Mennonite populations, French-Canadian populations, and Ashkenazi Jewish populations. For Old Order Mennonites, the prevalence is 1 in 380 births. In Ashkenazi Jews, the prevalence is 1 in 97 births. It is unknown what the prevalence is in the French-Canadian population. In these smaller populations that are the result of a founder effect, consanguinity is common. This results in a smaller gene pool and a recessive trait is passed on easily, such as this genetic disease.

Miranda Kaster--

Pregnancy Management (approved)

Control of metabolism is vital during pregnancy of women with MSUD. To prevent detrimental abnormalities in development of the embryo or fetus, dietary adjustments should be made and plasma amino acid concentrations of the mother should be observed carefully and frequently. Amino acid deficiency can be detected through fetal growth, making it essential to monitor development closely.^[6]

1. Strauss, Kevin A.; Puffenberger, Erik G.; Morton, D. Holmes (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C., eds. Maple Syrup Urine Disease. Seattle (WA): University of Washington, Seattle. PMID 20301495.

Diagnosis/Testing--Sara Russell

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. To diagnose MSUD clinicians will use tandem mass spectrometry to measure the whole blood combined leucine-isoleucine concentration and its ratio to other amino acids in the blood such as; alanine and phenylalanine. When diagnosing MSUD doctors will use the presence of clinical features such as; elevated BCAAs and allo-isoleucine in the newborns plasma. The newborn’s urine is also tested for hydroxyacids and ketoacids in the urine. Some doctors will use molecular genetic testing to determine if patients have Maple Syrup Urine Disease, but if this is not used another way to be able to diagnose Maple Syrup Urine Disease, it begins with biochemical testing.

Some biochemical tests that are used are;

Quantitative plasma amino acid analysis A lab can use quantitative plasma amino acid analysis to test for an increased plasma concentration of leucine. There also may be increased levels of plasma isoleucine and valine, but these levels can also be normal or even reduced. This test will also look for a plasma concentration of allo-isoleucine, which is a distinctive metabolite that is present in all types of Maple Syrup Urine Disease.

Tandem Mass Spectrometry (MS/MS)-based amino acid profiling This tandem mass spectrometry (MS/MS)-based amino acid profiling is done on the dried blood spots that were obtained during the newborn screening program between 24-48 hours old and this test quantifies whole blood concentration ratios of leucine+isoleucine to alanine and phenylalanine.

Urine Analysis In a child older than 48-72 hours urinary excretion of branched-chain alpha-hydroxyacids and alpha-ketoacids occurs in the urine. The gas chromatography-mass spectrometry test can identify large amounts of branched-chain ketoacids and branched-chain hydroxyacids in the urine and provides a quantitative amount. For a non-quantitative test the lab uses dinitrophenylhydrazine test, which is done by mixing the urine and dinitrophenylhydrazine reagent in equal amounts and then waiting 10 minutes for precipitate to form and this is scored from 0 to 4 based on the amount of precipitate formed. Lastly using standard urine strips the lab can test for ketonuria and can be used as a surrogate marker if there is not time to run the other tests.

Strauss, Kevin A.; Puffenberger, Erik G.; Morton, D. Holmes (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C., eds. Maple Syrup Urine Disease. Seattle (WA): University of Washington, Seattle. PMID 20301495.