Materiały źródłowe

• #1 Maple Syrup Urine Disease (MSUD) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/maple-syrup-urine-disease-msud

  Maple syrup urine disease is a rare inherited disorder caused by the bodys inability to properly process amino acids, leading to a characteristic odor of maple syrup in the baby’s urine. […] In most cases, MSUD is diagnosed at birth as part of routine newborn screening tests, which are required in many states. […] Most infants with MSUD are initially identified through newborn screening programs, then diagnosed with additional testing that may include: Blood and urine tests, ESI-Time of Flight mass spectrometry, to identify the levels of three specific amino acids leucine, isoleucine and valine in the blood, Genetic studies of the patient to identify any mutations of the BCKDHA, BCKDHB or DBT genes. […] If a family has a history of maple syrup urine disease, prenatal testing through chorionic villus biopsy or amniocentesis may be done to identify the disorder before birth, allowing clinicians to plan for early interventions as needed. […] For these reasons, its important to diagnose the disease as soon as possible and begin treatment.

• #2 Comprehensive Iranian guidelines for the diagnosis and management of maple syrup urine disease: an evidence- and consensus- based approach | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-025-03533-6

  Maple Syrup Urine Disease (MSUD) disease is a defect in the function of the Branched-chain 2-ketoacid dehydrogenase complex (BCKDH). […] This article considers pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and monitoring of MSUD patients with limited recourse. […] Diagnosis involves identifying elevated ratios of (leucine+isoleucine) to alanine and phenylalanine, increased levels of BCAAs, and alloisoleucine. In Iran, MSUD patients are identified through the NBS process leading to identifying more MSUD patients. […] MSUD should be suspected in asymptomatic patients with abnormal neonatal screening and/or symptomatic cases with clinical manifestations suspicious to MSUD. […] To diagnose this disease, various scenarios are considered: NBS for MSUD is primarily based on assessing the ratios of (leucine+isoleucine) to alanine and phenylalanine concentrations on dried blood spots.

• #2 Comprehensive Iranian guidelines for the diagnosis and management of maple syrup urine disease: an evidence- and consensus- based approach | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-025-03533-6

  Confirmation of Diagnosis in an MSUD suspicious patient is confirmed by the identification of biallelic pathogenic variants in one of the genes or limited cases by considerably decreased activity of the BCKD enzyme in leukocytes, cultured fibroblasts, or biopsied liver tissue. […] Molecular genetic testing is the preferred confirmatory test for MSUD.

• #3 Maple Syrup Urine Disease – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1319/

  Maple syrup urine disease (MSUD) is caused by decreased activity of the branched-chain alpha-ketoacid dehydrogenase complex (BCKD), the second enzymatic step in the degradative pathway of the branched-chain amino acids (BCAAs), which includes leucine, isoleucine, and valine. […] NBS for MSUD is primarily based on quantification of the ratios of (leucine + isoleucine) to alanine and phenylalanine concentrations on dry blood spots. A positive screening value (i.e., those above the cutoff reported by the screening laboratory) require follow-up biochemical testing with quantitative plasma amino acid and alloisoleucine analyses. If either is abnormal, treatment (see Management) and testing to establish the diagnosis (see Establishing the Diagnosis) should be initiated concurrently. […] The diagnosis of MSUD in a proband with suggestive metabolic/biochemical findings is established by identification of biallelic pathogenic (or likely pathogenic) variants in one of the genes listed in Table 1 or in limited instances by significantly reduced activity of the BCKD enzyme in cultured fibroblasts, leukocytes, or biopsied liver tissue. Because of its relatively high sensitivity, molecular genetic testing can obviate the need for enzymatic testing and, thus, is increasingly the preferred confirmatory test for MSUD.

• #4 Maple Syrup Urine Disease (MSUD) Workup: Laboratory Studies

  https://emedicine.medscape.com/article/946234-workup

  Routine newborn metabolic screening for maple syrup urine disease (MSUD) has been available since 1964. This screening is performed in all 50 United States and in various parts of the world. The test is performed within 24-48 hours following birth. Newborn screening for maple syrup urine disease is performed with tandem mass spectrometry (MS/MS) using concentrations of leucine and isoleucine and the Fisher ratio (branch-chain amino acids/phenylalanine and tyrosine) as diagnostic measures. Immediate treatment should follow the identification of affected newborn infants. […] The detection of l-alloisoleucine (also termed alloisoleucine) is diagnostic for maple syrup urine disease. A plasma l-alloisoleucine level greater than 5 mol/L is the most specific and most sensitive diagnostic marker for all forms of maple syrup urine disease.

• #4 Maple Syrup Urine Disease (MSUD) Workup: Laboratory Studies

  https://emedicine.medscape.com/article/946234-workup

  Molecular testing confirmation should be pursued in all patients diagnosed with maple syrup urine disease to confirm the diagnosis, to provide additional information about prognosis, to provide the knowledge for in-depth genetic counseling for the family, and to provide criteria for prenatal testing. […] Prenatal diagnosis can be performed by measuring BCKD enzyme activity in cultured amniocytes or chorionic villus cells, by performing mutation analysis, or by measuring branched-chain amino acid concentrations in amniotic fluid. However, molecular analysis is the most reliable and therefore preferred method for prenatal diagnosis.

• #5 Maple syrup urine disease – Wikipedia

  https://en.wikipedia.org/wiki/Maple_syrup_urine_disease

  Initially, the diagnosis was commonly made based on suggestive symptoms and odor, the odor coming from the compound sotolon. […] These days, affected individuals are now often identified by characteristic elevations on plasma amino acid which do not have the characteristic odor. […] The preferred prenatal diagnostic method is molecular analysis which requires a mutational analysis to measure BCKAD (branched-chain alpha-keto acid dehydrogenase) enzyme activity in chorion villus cells or amniocytes. Another measurement method is BCAA (branched-chain amino acid) concentration in amniotic fluids. […] On May 9, 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four further genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including maple syrup urine disease.

• #5 Maple syrup urine disease – Wikipedia

  https://en.wikipedia.org/wiki/Maple_syrup_urine_disease

  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. […] Other diagnostic methods include additional laboratory studies which include gas and liquid chromatography, BCKAD (branched-chain alpha-keto acid dehydrogenase) enzyme activity, dinitrophenylhydrazine (DNPH) test, and molecular testing. […] If a newborn screening was not performed, the result of the newborn screening is a false negative, or the newborn was not treated after a positive result, the clinical findings can be maple syrup odor twelve hours after birth. […] MSUD has five clinical phenotypes that are very distinct from one another. The most common and severe is the classical type with low residual activity from 0–2% of normal. Milder types include intermediate and intermittent with higher residual activities from 3–30% of the normal.

• #6 Maple syrup urine disease | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/maple-syrup-urine-disease

  Newborn screening for maple syrup urine disease is done using a small amount of blood collected from your babys heel. […] During screening, a special machine measures how much branched-chain amino acids are in your babys blood. Babies with high levels of the amino acids leucine, isoleucine, and/or valine might have maple syrup urine disease. […] If your babys blood spot screening result for maple syrup urine disease is out-of-range, your babys health care provider will contact you. Together, you will discuss next steps and follow-up plans. […] An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. […] Your baby may need the following tests after an out-of-range screening result: Blood and/or urine tests, Genetic testing using a blood sample.

• #6 Maple syrup urine disease | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/maple-syrup-urine-disease

  You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly. […] False-positive newborn screening results for this condition can happen. Babies who receive supplemental nutrition, also known as total parenteral nutrition (TPN) or hyperalimentation, may have false-positive screening results for maple syrup urine disease.

• #7

  https://www.gov.uk/government/publications/msud-suspected-description-in-brief/maple-syrup-urine-disease-msud-detailed-information

  Maple syrup urine disease, or MSUD, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Newborn screening allows the diagnosis of MSUD to be made early which can improve the long-term outcome. […] When your baby was about 5 days old, your midwife took some blood from your babys heel for their newborn blood spot screening test (the heel prick test). The newborn blood spot screening test measures the amount of some amino acids in the blood. A high level of the amino acid leucine suggests your baby may have MSUD. This is called a screen positive result. […] If your baby has a screen positive result, you will be contacted by the metabolic team and instructed to immediately take your baby to the local hospital for admission, even if they are well.

• #7

  https://www.gov.uk/government/publications/msud-suspected-description-in-brief/maple-syrup-urine-disease-msud-detailed-information

  Blood tests will be carried out to confirm if your baby has MSUD, but treatment will be started based on the screening result as the condition can be life-threatening. […] A metabolic crisis can lead to serious illness and long-term brain damage, and can be life-threatening. […] You should contact the metabolic team at the start of any illness to let them know your baby is unwell and that you have started the emergency regimen. […] Children from the same parents have a 1 in 4 chance of having MSUD. Your metabolic team will discuss if testing is necessary for your other children.

• #8 Newborn screening information for maple syrup urine disease | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/maple-syrup-urine-disease-msud

  Follow-up testing will involve checking your babys urine and blood samples for harmful amounts of acids and toxins. 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 babys body can help doctors determine if your baby has a condition. High amounts of branch-chained amino acids in the blood and ketones in the urine might indicate that your baby has MSUD. […] Healthcare professionals can learn more about confirmatory testing by reading the American College of Medical Genetics and Genomics’ Algorithm for Diagnosis and ACT Sheet, a guide for follow-up after newborn screening.

• #9 MSUDP – Overview: Maple Syrup Urine Disease Gene Panel, Varies

  https://www.mayocliniclabs.com/test-catalog/overview/608031

  Follow up for abnormal biochemical results suggestive of maple syrup urine disease (MSUD) […] Establishing a molecular diagnosis for patients with MSUD […] Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for maple syrup urine disease. […] The recommended first-tier screening tests for maple syrup urine disease (MSUD) are a combination of biochemical tests including quantitative plasma amino acids and urine organic acids. […] A comprehensive gene panel is a helpful tool to establish a diagnosis for patients with suggestive clinical and biochemical features given the broad clinical spectrum and genetic heterogeneity of MSUD. […] The BCKDH complex consists of 4 subunits (E1a, E1b, E2, E3), and this panel includes testing of the genes that encode each subunit (BCKDHA for E1a, BCKDHB for E1b, DBT for E2, and DLD for E3).

• #9 MSUDP – Overview: Maple Syrup Urine Disease Gene Panel, Varies

  https://www.mayocliniclabs.com/test-catalog/overview/608031

  The incidence of MSUD is approximately 1 in 185,000 live births in the general population. […] The recommended first-tier tests to screen for MSUD is a combination of biochemical tests including quantitative plasma amino acids (AAQP / Amino Acids, Quantitative, Plasma) to measure BCAA levels and alloisoleucine and urine organic acids (OAU / Organic Acids Screen, Urine) to look for presence of toxic urine metabolites including 2-hydroxy-isovaleric acid and 2-oxo-isocaprioic acid. […] Treatment of MSUD aims to normalize the concentration of BCAA by dietary restriction of these amino acids.

• #10 Challenges in Diagnosing Intermediate Maple Syrup Urine Disease by Newborn Screening and Functional Validation of Genomic Results Imperative for Reproductive Family Planning

  https://www.mdpi.com/2409-515X/7/2/25

  Maple syrup urine disease is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase, responsible for degradation of leucine, isoleucine, and valine. […] Newborn screening returned total leucine/isoleucine at the 99.5th centile of the population; however, as second-tier testing reported minimal alloisoleucine, the results were considered inconsistent with MSUD. […] A positive NBS result requires follow-up biochemical testing with quantitative plasma amino acid including alloisoleucine analyses. The presence of plasma alloisoleucine, above 5 μmol/L is the most sensitive and specific diagnostic marker for all forms of MSUD, with concentrations exceeding this value reported in 94% and 99.9% of patients with intermediate and classic forms of MSUD, respectively. […] Elevated BCAAs and alloisoleucine on quantitative plasma amino acid profiling provides diagnostic confirmation of MSUD.

• #10 Challenges in Diagnosing Intermediate Maple Syrup Urine Disease by Newborn Screening and Functional Validation of Genomic Results Imperative for Reproductive Family Planning

  https://www.mdpi.com/2409-515X/7/2/25

  It has been suggested that in vitro measurements of BCKD activity are discordant with in vivo leucine oxidation rates or dietary leucine tolerance, hence are not clinically useful. […] However, these results from leucine decarboxylation studies in fibroblasts concur with the clinical phenotype of intermediate MSUD, hence indicating the potential usefulness of such studies in classifying clinical phenotypes. […] The majority of individuals with intermediate MSUD are detected by NBS, although later diagnosis can occur when newborns are not screened for MSUD. […] This case further substantiates the reversibility of neurological insults sustained during acute decompensation, also reported in other patients where complete resolution of neuroimaging abnormalities has occurred concurrently with normalisation of BCAA levels.

• #10 Challenges in Diagnosing Intermediate Maple Syrup Urine Disease by Newborn Screening and Functional Validation of Genomic Results Imperative for Reproductive Family Planning

  https://www.mdpi.com/2409-515X/7/2/25

  Importantly, this report highlights the challenges faced in identifying non-classical forms of MSUD through NBS. […] The subsequent diagnosis of this patient prompted further review of MSUD follow-up procedures, and several service improvements were implemented. […] Advances in genomic sequencing technologies have resulted in the increasing discovery of novel disease-causing genes or rare variants, with the consequent need for orthogonal functional studies to validate their mutational impact and pathogenicity. […] The variants in this 5-month-old girl with biochemical results consistent with MSUD demonstrate the importance of performing functional assays to validate pathogenicity and reclassification of these variants. […] Use of BCAA ratios as part of second-tier and diagnostic testing can improve the detection of non-classical MSUD forms.

• #11 Maple syrup urine disease – Genomics Education Programme

  https://www.genomicseducation.hee.nhs.uk/documents/maple-syrup-urine-disease/

  Biochemical testing for the diagnosis of MSUD includes quantitative plasma amino acid and urine organic acid analysis, typically performed by specialist metabolic laboratories. […] In MSUD patients, amino acid analysis is used to detect the characteristic elevation in plasma leucine concentrations. Isoleucine and valine are typically also elevated, but may be normal or low. An elevated plasma allo-isoleucine concentration is diagnostic for MSUD. […] Organic acid analysis is used to support the diagnosis by identifying elevated branched-chain keto- and hydroxy-acids in the urine. […] MSUD may also be diagnosed by tandem mass-spectrometry analysis of leucine in dried blood spots, as part of a newborn screening programme. This analysis is part of the NHS newborn blood spot screening (NBS) programme in England.

• #12 Maple Syrup Urine Disease and Other Disorders of Branched Chain Amino Acid Catabolism | myadlm.org

  https://myadlm.org/science-and-research/clinical-chemistry/clinical-chemistry-trainee-council/pearls-of-laboratory-medicine-in-english/2019/maple-syrup-urine-disease-and-other-disorders-of-branched-chain-amino-acid-catabolism

  MSUD is inherited in an autosomal recessive fashion and estimated to have a worldwide prevalence of 1 in 185,000, with an increased frequency in Mennonite populations. […] A positive newborn screen or recognition of symptoms such as poor feeding, irritability, ketonuria, opisthotonos, and fencing or bicycling-like movements should prompt biochemical studies such as plasma amino acids and urine organic acid profiles. […] While newborn screening is useful for the early detection of MSUD, definitive diagnosis is made by identifying the clinical features of the disease, plasma amino acid quantification, and urine organic acid profiles. Hallmark elevations in BCAAs are observed in the plasma of individuals with classic and intermediate MSUD. […] Therefore, the identification of persistently elevated leucine, and alloisoleucine concentrations 5 mol/L, are pathognomonic for the disease.

• #13 Maple Syrup Urine Disease | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/24737

  MSUD occurs due to a pathogenic defect in any BCKAD subunit, resulting in elevated branched-chain amino acids and their corresponding alpha keto-acids. […] Since MSUD is often rapidly progressive and can cause permanent harm within the first few weeks of life, it has become routine to perform diagnostic testing for MSUD on all newborns within 48 hours of birth. […] Diagnosis requires mutational analysis to measure BCKAD enzyme activity in cultured chorion villus cells or amniocytes. […] Since 1964, routine newborn screening has been performed for MSUD in the United States. […] Plasma amino acid testing is the most critical and reliable diagnostic test for MSUD. […] The molecular tests available to determine the 3 biallelic pathogenic gene variants include the BCKDHA gene which encodes the E1-alpha subunit of the BCKAD enzyme complex (MSUD Type 1A), BCKDHB gene which encodes the E1-beta subunit of the BCKAD enzyme complex (MSUD Type 1B), and the DBT gene which encodes the E2 subunit of the BCKAD enzyme complex (MSUD Type 2).

• #13 Maple Syrup Urine Disease | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/24737

  In symptomatic adults, diagnostic evaluation should include the following: DNPH testing can be used for the detection of alpha-ketoacids in the urine. […] The most definitive, informative, and reliable test is the identification of elevated serum alloisoleucine using plasma amino acid quantitative analysis. […] In symptomatic newborns with a positive screening test or unexplained ketonuria, diagnostic evaluation should include the following: Plasma amino acid analysis to detect elevated BCAA and alloisoleucine. […] Confirmatory testing for MSUD is most reliably done by plasma amino assay analysis, which cannot be performed before 6 days after birth.

• #14 Symptoms of Maple Syrup Urine Disease: Life Expectancy, Causes

  https://www.medicinenet.com/what_are_the_symptoms_of_maple_syrup_urine_disease/article.htm

  Genetic testing: This can confirm the diagnosis of MSUD by detecting mutations in the genes that are responsible for the disorder. This testing is usually done after the diagnosis is confirmed through urine and blood tests. […] Molecular testing: A type of genetic testing that can identify specific mutations in the genes responsible for MSUD. This type of testing is useful for families with a history of the disease or individuals who have already been diagnosed with MSUD and want to know the specific genetic mutation responsible for their condition. […] Enzyme assays: Enzyme assays are a type of biochemical test that measures the activity of enzymes in the body. In MSUD, the activity of the enzyme responsible for breaking down the amino acids is reduced or absent. Enzyme assays can help confirm the diagnosis of MSUD. […] It is important to diagnose MSUD early to begin treatment promptly and prevent serious complications.

• #15 Decoding Intermediate Maple Syrup Urine Disease Type 2: A Dive into Genetic Testing and Diagnosis

  https://sequencing.com/education-center/medical/intermediate-maple-syrup-urine-disease-type-2?srsltid=AfmBOopMrhZwfCeMib0tCMWssuYcsIZT8iJNXvLz7iY_-8XxE2ZrKoUr

  Diagnosing intermediate MSUD type 2 can be challenging due to its variable presentation and the rarity of the condition. […] This highlights the importance of genetic testing in diagnosing ambiguous cases of MSUD. […] Genetic testing for MSUD involves analyzing the DNA for mutations in the genes responsible for the production of BCKD. Identifying the specific gene mutations can help confirm the diagnosis, determine the severity of the disease, and guide treatment decisions. […] In conclusion, genetic testing plays a pivotal role in understanding, diagnosing, and managing intermediate maple syrup urine disease type 2. Early detection and intervention are crucial for improving the quality of life for those affected by this rare metabolic disorder.

• #16 Maple Syrup Urine Disease: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21168-maple-syrup-urine-disease

  Healthcare providers diagnose classic MSUD with newborn screenings (blood tests) soon after a baby is born. Prenatal testing can show if the fetus has classic MSUD. Depending on how far along you are in your pregnancy, providers test a tissue sample from the placenta (chorionic villus sampling) or amniotic fluid (amniocentesis). […] Children with intermediate, intermittent, or thiamine-responsive MSUD might not show signs of the disease until their toddler years or early childhood. In these cases, providers diagnose MSUD with metabolic blood tests and genetic testing. Evaluating your child’s symptoms (recognizing the distinctive sugar/maple smell of their sweat, urine or earwax) may give clues to the diagnosis.

• #17 Maple syrup urine disease: mechanisms and management | TACG

  https://www.dovepress.com/maple-syrup-urine-disease-mechanisms-and-management-peer-reviewed-fulltext-article-TACG

  Subsequent quantitative plasma amino acid profiling that includes alloisoleucine detection provides the strongest evidence supporting a diagnosis of MSUD. […] Urine organic acid analysis by GC-MS/MS to detect BCKA (including -ketoisocaproate, -keto–methylisovalerate, -ketoisovalerate) also provides supporting evidence for a diagnosis of MSUD. […] The milder variant forms of MSUD are often missed by NBS due to normal leucine levels in the newborn period. […] All classic MSUD patients have pathognomonic elevations of alloisoleucine; however, even second-tier testing can miss variant cases, which may only be detectable during acute illness or metabolic crises.

• #18 Maple syrup urine disease

  https://www.nhs.uk/conditions/maple-syrup-urine-disease/

  If your child becomes ill, they might have an episode of a metabolic crisis. This can lead to serious illness and long-term brain damage, and can be life threatening. […] Take your child to hospital if the symptoms of a metabolic crisis develop, if they cannot keep down their emergency diet and supplements, or they have repeated diarrhoea. […] A liver transplant is sometimes an option to treat MSUD. If a person with MSUD receives a donated liver, they’ll no longer be at risk of a metabolic crisis and can have a normal diet. […] Although it’s not possible to prevent MSUD, it’s important to let your midwife and doctor know if you have a family history of the condition, so that tests and treatment are given as soon as possible.

• #18 Maple syrup urine disease

  https://www.nhs.uk/conditions/maple-syrup-urine-disease/

  At around 5 days old, babies are offered newborn blood spot screening to check for inherited conditions like MSUD. This involves pricking your baby’s heel to collect drops of blood to test. […] If your baby is diagnosed with MSUD, treatment should be given straight away to reduce the risk of serious complications. With early diagnosis and the correct treatment, the outcome can be greatly improved. However, treatment for MSUD must be continued for life. […] It’s important to get medical help immediately if your baby develops symptoms of a metabolic crisis. Your doctor will give you advice to help you recognise the signs. […] Children diagnosed with MSUD are first referred to a specialist metabolic dietitian and given a low-protein diet. […] Some children need to take supplements of isoleucine and valine alongside the prescribed diet. This helps to maintain a healthy level of these amino acids in the blood without causing harm. Blood tests are needed to monitor these levels.

• #19 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease (MSUD), also known as branched-chain ketoaciduria, is an aminoacidopathy due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Early diagnosis and dietary intervention prevent complications and may allow for normal intellectual development. Consequently, maple syrup urine disease has been added to many newborn screening programs, and preliminary results indicate that asymptomatic newborns with maple syrup urine disease have better outcomes compared with infants who are diagnosed after they become symptomatic. […] Morbidity can almost entirely be prevented with early diagnosis (in a neonate younger than 10 days), with appropriate treatment at presentation and during episodes of potential metabolic decompensation. […] Diagnosis and treatment of maple syrup disease: a study of 36 patients. […] Diagnosis of MSUD by newborn screening allows early intervention without extraneous detoxification.

• #20 Maple syrup urine disease | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/maple-syrup-urine-disease?lang=us

  Maple syrup urine disease (MSUD) is a very rare metabolic disorder. It is an inborn error of amino acid metabolism, which classically affects the brain tissue resulting in impairment or death if untreated. […] There is elevated plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine), allo-isoleucine, and alpha-ketoacids. […] Management involves dietary changes, such as life-long dietary intake restriction of foods with branched-chain amino acids (especially leucine), and early treatment of metabolic decompensation, with agents such as intravenous glucose.

• #21 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  In the classical form of maple syrup urine disease, infants appear well at birth. Symptoms begin after 3 to 5 days and progress rapidly to death within 2 to 4 weeks if branched-chain amino acid restriction is not implemented. […] Diagnosis for all forms is best made before irreversible clinical damage is produced through population-based newborn screening. In the symptomatic child, the smell of burnt sugar or maple syrup may be manifest in urine, sweat, or ear wax. […] Diagnosis is made by quantitative and qualitative analysis of plasma and urine L-leucine, L-isoleucine, alloisoleucine, and L-valine. Low plasma glutamine can be noted. Gas chromatography of urine will reveal the branched-chain alpha-ketoacids (alpha-ketoisocaproate, alpha-keto-beta methylvaleric, and alpha-ketoisovaleric acids) as well as their hydroxy derivatives when patients are in poor dietary control.

• #21 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  The first pathognomonic sign of maple syrup urine disease may be the sweet-smelling diaper or cerumen at the tip of the otoscope. A bedside diagnosis could be made using the dinitrophenylhydrazine reaction on a few milliliters of urine. On about 1.0 mL of heparinized blood, quantitation of plasma amino acids will lead to a diagnosis. Normal, early-childhood ranges of L-leucine, L-isoleucine, and L-valine concentrations in plasma are 29 to 151 M, 20 to 96 M, and 67 to 299 M, respectively. […] Evaluation of urinary organic acids by gas chromatography and mass spectrometry will virtually diagnose maple syrup urine disease and enable immediate dietary intervention.

• #22 Symptoms And Signs Of Maple Syrup Urine Disease – Klarity Health Library

  https://my.klarity.health/symptoms-and-signs-of-maple-syrup-urine-disease/

  Early diagnosis and treatment of MSUD symptoms are critical since they can avert serious health problems. […] Babies undergoing newborn screening tests, performed soon after birth, are able to identify MSUD before symptoms manifest. […] This distinctive odour is a critical clue for detecting the disease quickly. […] Early diagnosis of serious genetic abnormalities, such as Maple Syrup Urine Disease (MSUD), is mostly dependent on newborn screening. […] A heel prick blood test is one of the techniques used, and the sample is examined for certain metabolites and enzyme activity that may indicate metabolic abnormalities. […] Elevated leucine, isoleucine, and valine levels are commonly seen in MSUD. […] When a newborn screening test yields a positive result initially, more testing is necessary to confirm the diagnosis. […] Genetic testing entails sequencing the genes linked to MSUD. […] Knowledge of the family history is crucial to the diagnosis.

• #23 Maple Syrup Urine Disease | American Journal of Neuroradiology

  https://www.ajnr.org/ajnr-case-collections-diagnosis/maple-syrup-urine-disease-0

  Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder of branched chain amino acids caused by a defect in the oxidative decarboxylation of branched-chain -keto acids (BCKA). […] Key Diagnostic Features: Restricted diffusion in the deep cerebellar white matter, dorsal brainstem, cerebral peduncles, posterior limb of internal capsule and centrum semiovale. Cerebral edema is also seen. Inadequate therapy results in generalized volume loss and periventricular hyperintensities on T2-weighted MRI.

• #24

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

  The classic form, which comprises 75% of MSUD patients, is manifested within the first 2 weeks of life with poor feeding, lethargy, seizures, coma, and death if untreated. Intermediate MSUD is associated with elevated BCAAs and BCKA, with progressive mental retardation and developmental delay without a history of catastrophic illness. The diagnosis is usually delayed for many months. An intermittent form of MSUD may have normal levels of BCAAs, normal intelligence and development until a stress, e.g., infection, precipitates decompensation with ketoacidosis and neurologic symptoms, which are usually reversed with dietary treatment. Thiamine-responsive MSUD is similar to the intermediate phenotype but responds to pharmacologic doses of thiamine with normalization of BCAAs. […] The authors emphasized the importance of diagnosis within the first days of life and concluded that classic MSUD can be properly managed to allow a benign neonatal course, normal growth and development, and low hospitalization rates.

• #25 Orphanet: Intermittent maple syrup urine disease

  https://www.orpha.net/en/disease/detail/268173

  Intermittent MSUD may be missed on tandem mass spectrometry newborn screening. BCAA levels are usually normal or only slightly elevated, except during times of physiological stress when the biochemical profile is similar to classic MSUD. Ketonuria and gas chromatography-mass spectrometry can also identify branched-chain alpha ketoacids (BCKAs) in the urine during decompensation only. […] Prenatal diagnosis is possible in families with a known disease-causing mutation. […] Inheritance is autosomal recessive and genetic counseling is possible. […] Management of acute decompensation requires aggressive enhancement of protein anabolism which may include using glucose plus insulin, intravenous lipids, plasma amino acid monitoring, and isoleucine and valine supplements.

• #26 Maple syrup urine disease diagnosed in a resource-limited setting in an infant in Nepal: a case report | BMC Pediatrics | Full Text

  https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-05266-0

  The advent of tandem mass spectrometry (MS/MS) has expedited the timely diagnosis of metabolic disorders initiating early interventions. […] The identification of suspicious MSUD in our case is only based on qualitative screening and mass spectrometric analysis. […] It is high time early diagnosis and interventions of these preventable congenital disorders are brought up to be noticed publicly and addressed at policy levels. […] Studies illuminate that if MSUD is detected by the 11th day, dietary regulation and careful monitoring of urinary keto-acid concentration can control the condition with a better prognosis. […] However, in Nepal due to a lack of advanced techniques, the late diagnosis as well as financial restrictions in enduring formulated diet results in increased mortality in IEMs. […] Therefore, keeping into account the gravity of problem, metabolic screening should be prioritized in national policies along with efforts in its management to ameliorate the neonatal mortality rates.

• #27 Expanding the genotypic and phenotypic spectrum of Egyptian children with maple syrup urine disease | Scientific Reports

  https://www.nature.com/articles/s41598-024-78105-y

  Maple Syrup Urine Disease (MSUD, OMIM# 248600) is an autosomal recessive inborn error of metabolism characterized by elevated branched chain amino acids (BCAA) leucine/isoleucine and valine in blood of affected children. […] We performed Sanger sequencing for the three most-commonly responsible genes: BCKDHA, BCKDHB and DBT and conducted exome sequencing for unresolved cases. […] Through Sanger sequencing, we detected eight homozygous pathogenic/likely pathogenic variants (four in BCKDHB, three in BCKDHA and one in DBT gene) in eight different families. […] With a biochemical evidence of elevated BCAAs in blood, Sanger sequencing of the most commonly affected genes; BCKDHA, BCKDHB and DBT often reveals the genetic background of MSUD. […] Molecular diagnosis is also critical to confirm affected individuals and carriers of the disease, which is highly important for prenatal diagnosis and premarital genetic counseling in affected families.

• #27 Expanding the genotypic and phenotypic spectrum of Egyptian children with maple syrup urine disease | Scientific Reports

  https://www.nature.com/articles/s41598-024-78105-y

  We conducted this study for investigating the genetic spectrum of 10 Egyptian pediatric patients with clinical features suggestive of MSUD and elevated BCAAs in blood spots detected by tandem mass spectrometry. […] Sanger sequencing of BCKDHA, BCKDHB and DBT genes conducted for the nine affected families revealed eight different homozygous pathogenic/likely pathogenic variants (four in BCKDHB, three in BCKDHA and one in DBT gene). […] In family VI (Proband 7), Sanger sequencing didn’t detect any pathogenic/likely pathogenic variants in the three genes, thus an extensive sequencing technique (exome sequencing) was performed for the proband of this family in a trial to reveal his genotype. […] Genetic testing of causative genes in MSUD is crucial to confirm the diagnosis and provide proper genetic counseling and prenatal diagnosis for the affected families.

• #28 Newborn Screening Program – Maple Syrup Urine Disease

  http://www.idph.state.il.us/healthwellness/fs/msud.htm

  Maple syrup urine disease (MSUD) is an inherited disorder of amino acid metabolism, caused by a deficiency in an enzyme complex that results in defects in the catabolism of the amino acids leucine, isoleucine and valine. […] In Illinois, newborn screening for MSUD is performed using tandem mass spectrometry. False positive and false negative results are possible with this screening. Infants with a presumptive positive screening tests require prompt follow-up and, when notified of these results, the clinician should immediately check on the clinical status of the baby and refer the infant to a metabolic disease specialist. […] Early diagnosis and prompt treatment can significantly affect prognosis. […] These guidelines should be followed after a diagnosis of MSUD has been confirmed: Parents should understand that treatment is lifelong and that compliance with dietary management is imperative to the child’s health, growth and development. Infants and children with MSUD should have regular follow-up appointments with a metabolic disease specialist. Long-term management, monitoring and compliance with treatment recommendations are essential to the child’s well-being. A multi-disciplinary approach including the following specialties is recommended: pediatrics, genetics and nutrition. Parents should understand that treatment is not curative and that all morbidity cannot necessarily be prevented. Genetic counseling services are recommended.

• #29 Amino Acids, Maple Syrup Urine Disease Panel, Plasma – Essentia Health Lab Services

  https://essentiahealth.testcatalog.org/show/AAMSD

  Test Code AAMSD Amino Acids, Maple Syrup Urine Disease Panel, Plasma […] Follow-up of patients with maple syrup urine disease […] Monitoring of dietary compliance for patients with maple syrup urine disease […] Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by the deficiency of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. […] Treatment of MSUD aims to normalize the concentration of BCAA by dietary restriction of these amino acids. […] The quantitative results of isoleucine, leucine, valine, and allo-isoleucine with age-dependent reference values are reported without added interpretation.

• #30 Amberly’s journey with Maple Syrup Urine Disease: From diagnosis to liver transplant

  https://www.manningchildrens.org/news-blog/2024/november/amberlys-journey-with-maple-syrup-urine-disease-/

  While maple syrup urine disease isnt specifically an isolated liver condition, it is a genetic disorder that affects amino acid metabolism throughout the body, explained Dr. Arias. The liver plays a crucial role in this process, and a liver transplant is the only definitive cure. It provides a functioning copy of the enzyme needed to break down amino acids, correcting the metabolic imbalance caused by the deficiency. […] Prior to her transplant, Amberly underwent a series of blood tests to confirm compatibility and ensure her body was ready for the procedure. These tests also checked her overall health and ruled out any infections or complications. […] Amberly also required stents in her bile ducts after the transplant to help with proper drainage which was performed by Russell Zwiener, MD, a pediatric advanced endoscopist at Childrens Hospital. […] Today, Amberly is thriving post-transplant. She follows a strict regimen of anti-rejection medications and has bloodwork done every two weeks near their home in Baton Rouge.

• #31 Maple syrup urine disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/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. […] Maple syrup urine disease is often classified by its pattern of signs and symptoms. […] Genetic Testing Registry: Classical maple syrup urine disease […] Genetic Testing Registry: Maple syrup urine disease […] This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. […] Researchers are studying other genes related to the same protein complex that may also be associated with maple syrup urine disease.

• #32 Maple syrup urine disease (MSUD) | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/maple-syrup-urine-disease-msud

  Newborn screening for MSUD is crucial for early diagnosis and management, as timely intervention can significantly improve outcomes. […] Testing should be done within the first twenty-four hours after birth, since early diagnosis is essential. […] The detection of alloisoleucine is diagnostic for MSUD but may not appear until the sixth day of life. […] Carrier testing is available for the Mennonite variant of the disease.

• #33 Orphanet: Maple syrup urine disease

  https://www.orpha.net/en/disease/detail/511

  A rare inherited disorder of branched-chain amino acid metabolism classically characterized by poor feeding, lethargy, vomiting and a maple syrup odor in the cerumen (and later in urine) noted soon after birth, followed by progressive encephalopathy and central respiratory failure if untreated. […] The estimated prevalence is around 1/150,000 live births, from published and unpublished newborn screening data. […] MSUD follows an autosomal recessive inheritance pattern and genetic counseling is possible.

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