Materiały źródłowe

• #1 Maple Syrup Urine Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557773/

  MSUD has an estimated worldwide incidence of just 1 case per 185,000 live births. For perspective, the Health Resources and Services Administration estimates only 30 new neonatal cases a year are diagnosed in the United States. Higher occurrences have been noted in populations with a higher rate of consanguinity. MSUD affects males and females equally. In the Ashkenazi Jewish population, the incidence is estimated at 1 in 26,000 live births. In Mennonites, MSUD occurs with an incidence of 1 in 380 newborns. This is often termed a „founder effect” in the BCKDHA (E1a) gene. In the Portuguese Romani population, incidence is estimated at 1 case per 71 births.

• #2 Overview of maple syrup urine disease – UpToDate

  https://www.uptodate.com/contents/overview-of-maple-syrup-urine-disease

  MSUD occurs in approximately 1 in 86,800 to 185,000 live births. The MSUD incidence is up to 1:200 live births in certain Mennonite populations in Pennsylvania and elsewhere due to a founder variant (c.1312T>A) in the branched-chain ketoacid dehydrogenase complex gene (BCKDHA). […] Founder variants are identified in populations with a particularly high prevalence of MSUD (eg, Mennonites, Amish).

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

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

  Maple syrup urine disease occurs in about 1 case per 185,000 live births. Within the Ashkenazi Jewish population, the incidence is higher, at 1 per 26,000 live births. In select inbred populations (ie, the Mennonites in Pennsylvania), it may be as common as 1 case per 176 newborns. As an autosomal recessive disorder, maple syrup urine disease is more prevalent in populations with a high occurrence of consanguinity. […] Quental et al identified a homozygous 1-bp deletion (117delC) in the BCKDHA gene (this gene codes for the alpha subunit of the BCKD enzyme complex, specifically E1) in Portuguese Gypsies and estimated the carrier frequency for this deletion to be as high as 1.4% (about 1 case per 71 live births). […] Infants with untreated early onset (ie, classic) maple syrup urine disease have significant developmental delay and die within the first months of life. Children or juveniles with late-onset (ie, intermediate, intermittent) forms of maple syrup urine disease may have some form of developmental delay, depending on the residual enzyme activity of BCKD. All children are at increased risk for metabolic decompensation during periods of increased protein catabolism (eg, intercurrent illness, trauma, surgery). 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. […] Maple syrup urine disease has been reported to occur in all ethnic groups, although the incidence and prevalence may widely vary. […] No sex predilection is noted, as the genetic case is autosomal recessive and not related to the sex chromosomes.

• #4 Maple syrup urine disease | Newborn Screening

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

  It is estimated that fewer than 30 babies are born with this condition each year in the United States. […] Newborn screening for maple syrup urine disease is done using a small amount of blood collected from your baby’s heel. […] Babies with high levels of the amino acids leucine, isoleucine, and/or valine might have maple syrup urine disease. […] Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly. […] 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.

• #5 Incidence of maple syrup urine disease, propionic acidemia, and methylmalonic aciduria from newborn screening data

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6047110/

  Incidence for the branched-chain intoxication-type disorders, maple syrup urine disease, propionic acidemia and methlymalonic aciduria is dependent on the population screened. Here newborn screening results from three world regions, state screening laboratories in the United States, a region in Germany and Kuwait provides new incidence numbers. Maple syrup urine disease incidence in the United States was calculated to be 1: 220219, in South-West Germany 1: 119573 (Germany nationwide 1:177978), and in Kuwait 1: 59426. […] We recognize that incidence of metabolic disorders are impacted by ascertation bias, population frequencies, and screening methods and so set out to use publicly available newborn screen data to determine whether we could calculate the incidence of MSUD, MMA, and PA for several populations. We found that there is most certainly a difference in incidence across populations and so it is best to recognize the risk within the population treated.

• #6 Maple syrup urine disease – Genomics Education Programme

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

  Approximately 1 in 116,000 infants are affected by the condition in the UK. […] 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.

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

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

  In most cases, MSUD is diagnosed at birth as part of routine newborn screening tests, which are required in many states. Pennsylvania, New Jersey and Delaware all require newborn screening for maple syrup urine disease. […] MSUD is believed to affect 1 in 185,000 births worldwide. MSUD is more common in the Mennonite population in comparison to the general population. MSUD is believed to affect 1 in 380 people in the Old Order Mennonite population and 1 in 26,000 in the Ashkenazi Jewish population. About 2,000 people in the U.S. have been diagnosed with MSUD. […] Most infants with MSUD are initially identified through newborn screening programs, then diagnosed with additional testing that may include: […] 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. […] MSUD can cause irreversible metabolic damage and be life-limiting. For these reasons, its important to diagnose the disease as soon as possible and begin treatment.

• #8 Maple syrup urine disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/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, with an estimated incidence of about 1 in 380 newborns. […] DNA carrier testing and newborn screening for maple syrup urine disease in Old Order Mennonite communities.

• #9 RFTS – Home Page

  https://www.wvdhhr.org/nbms/diseases/Maple_Syrup_Urine_Disease.asp

  Maple syrup urine disease (MSUD) (OMIM database No. 248600),108 also known as branched-chain ketoaciduria, is caused by a deficiency in activity of the branched-chain {alpha}-keto acid dehydrogenase (BCKD) complex. […] The worldwide frequency of MSUD (including classic and some variant forms), which is based on routine screening data from 26.8 million newborn infants, is approximately 1 in 185000.109,110 Newborn screening of 756163 newborn infants over an 8-year period in Georgia revealed a much higher frequency of 1 in 84000.111 In the population of Mennonites living in Lancaster and Lebanon counties in Pennsylvania, the incidence is 1 in 176 newborn infants, most likely attributable to a founder effect.112,113 […] State-of-the-art screening for MSUD is by MS/MS. The sum of the 3 isomers (leucine, isoleucine, and alloisoleucine) leads to a distinct diagnostic peak.109 Classic MSUD, the intermediate form, and E3 deficiency can usually be detected by screening in the newborn period. Intermittent MSUD would not be detected, because the patients’ concentrations are normal when they are not in crisis. Thiamine-responsive MSUD has been missed by newborn screening.110

• #10 Reddit – The heart of the internet

  https://www.reddit.com/r/todayilearned/comments/ue4e1d/til_about_maple_syrup_urine_disease_a_disorder/

  TIL about Maple Syrup Urine Disease, a disorder whose name is attributed to the smell of maple syrup in affected peoples’ urine. It leads to death if untreated and is prevalent in about 1 in 180,000 live births in the US. However, for the Amish and Mennonites, the frequency is 1 in 176 live births.

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

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

  MSUD is very rare. It affects about 1 in every 185,000 babies born worldwide. […] It occurs more often in populations with a small gene pool or when close relatives have children together. For example, MSUD is more common among Mennonites in the United States (1 in every 380 births), where community members often marry and have kids. Its also more common in the Ashkenazi Jewish population (1 in every 26,000 births).

• #12 Overview of maple syrup urine disease – UpToDate

  https://www.uptodate.com/contents/overview-of-maple-syrup-urine-disease/print

  Maple syrup urine disease (MSUD; MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids (BCAAs). It is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway of the three BCAAs, leucine, isoleucine, and valine. It is characterized by psychomotor delay, feeding problems, and a maple syrup odor of the urine. […] MSUD occurs in approximately 1 in 86,800 to 185,000 live births. The MSUD incidence is up to 1:200 live births in certain Mennonite populations in Pennsylvania and elsewhere due to a founder variant (c.1312T>A) in the branched-chain ketoacid dehydrogenase complex gene (BCKDHA). […] Founder variants are identified in populations with a particularly high prevalence of MSUD (eg, Mennonites, Amish).

• #13 Maple Syrup Urine Disease – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/maple-syrup-urine-disease/

  MSUD is thought to affect approximately 1 person in every 100,000 in the UK and 1 person in every 185,000 worldwide. […] MSUD is a serious inherited metabolic disorder that can lead to severe brain damage. Damage can be prevented with a protein restricted diet, a protein substitute and appropriate illness management. During illness, it is imperative that emergency feeds are started promptly, followed strictly and there are no delays in management. Regular blood tests are essential to monitor the management of MSUD.

• #14 Maple syrup urine disease (MSUD)

  https://www2.hse.ie/conditions/heel-prick-screening/conditions/maple-syrup-urine-disease/

  Around 1 in 155,200 babies born in Ireland have MSUD. […] Milder forms of MSUD may not be detected by screening, because the condition can start later in life.

• #15 Maple Syrup Urine Disease | Newborn Screening Ontario

  https://www.newbornscreening.on.ca/en/results/screen-positive-results/disease-information/maple-syrup-urine-disease/

  Approximate incidence in Ontario: 1 in 200,000. […] Screening is important. […] In Ontario, a heel prick is used to take a few drops of blood from each baby shortly after birth. The blood is tested for more than 25 treatable diseases, including MSUD. […] Follow-up testing is important to find out whether the baby truly has MSUD. […] Babies with MSUD are healthier if treatment begins early. […] Follow-up testing is arranged as soon as possible and involves blood and sometimes urine tests. […] Screening and treatment aim to prevent metabolic crises and help children with MSUD live healthier lives. […] Early treatment often allows babies with MSUD to lead healthy lives with normal growth and intelligence.

• #16 Maple Syrup Urine Disease (MSUD)

  https://mdda.org.au/diagnosis/maple-syrup-urine-disease/

  1:150,000 babies born in Australia and New Zealand.

• #17 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) happens in about 1 in 86,800 to 185,000 live births. […] The prevalence of this disease is reported to be higher in countries where consanguineous marriage is more common (1 in 50,000 in Turkey). […] We do not have accurate information on disease prevalence in Iran. […] In Iran, MSUD patients are identified through the NBS process leading to identifying more MSUD patients. […] The NBS was performed in some parts of Iran for 20 Inborn Errors of Metabolism (IEM). […] All newborn neonates are screened for 20 inherited metabolic diseases three to five days after birth. […] This article provides a guideline that can be useful for all physicians, primary care providers, and other specialists who often are involved in the care of individuals with MSUD in Iran and other countries with the same situation of laboratory and therapeutic material. […] The challenges in the management and screening of MSUD faced in Iran are mentioned.

• #18 Maple Syrup Urine Disease – CAGS

  https://cags.org.ae/en/ctga-details/199/maple-syrup-urine-disease

  Maple Syrup Urine Disease (MSUD) is a recessively inherited inborn error of metabolism characterized by the inability to metabolize the branched chain amino acids leucine, isoleucine, and valine, hence, resulting in their accumulation in the blood. […] In 2006, Al-Arrayed indicated that MSUD occurs in Bahrain at an approximate incidence of 2/10,000 births. […] The Centre for Arab Genomic Studies Work Group (2006) conducted a retrospective study for metabolic disorders described at AlWasl Hospital in Dubai between 1997 and 2006. Only two cases of MSUD were observed in Jordanian (one male and one female) residents of the UAE. […] Joshi et al, 2002, carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between 1998 and 2000. Among the 82 patients, one was diagnosed with MSUD [CTGA Database Editor’s note: Computed annual incidence rate is 0.8/100,000].

• #19 Maple Syrup Urine Disease – ORD India

  https://ordindia.in/maple-syrup-urine-disease/

  Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide. The disorders estimated incidence is about 1 in 380 newborns, occurring much more frequently in the Old Order Mennonite population. The prevalence of MSUD is 1 in 100,000 in India. […] Newborn screening programs also help in detecting MSUD. Tandem mass spectrometry has aided in the diagnosis of MSUD by measuring BCAAs levels. Similar to all inborn errors, infants with mild forms of the disorder can be missed by newborn screening as their amino acid levels may remain within normal range initially.

• #20 Exploring molecular spectrum in thai patients with maple syrup urine disease: unveiling a common variant | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03411-7

  Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand. […] The incidence of MSUD varies across different ethnicities, with an overall reported rate of 1 in 185,000 live births. For instance, Mennonite populations exhibit a notably higher incidence, estimated at 1 in 380 live births. In Spain, the incidence ranges between 1 in 12,000-50,000 live births, while in Portugal, it is reported to be approximately 1 in 86,800 live births.

• #21 Maple Syrup Urine Disease – CAGS

  https://cags.org.ae/en/ctga-details/199/maple-syrup-urine-disease

  In 2003, the Hamad Medical Corporation, in partnership with the University Children’s Hospital of Heidelberg, built a comprehensive newborn screening program. Between December 2003 and July 2006, Lindner et al, 2007, investigated 25,214 neonates born in Qatar for inborn errors of metabolism and endocrine disorders. Two neonates were diagnosed with MSUD. […] During a period of three years nearly 14 cases of MSUD were observed; suggesting an alarmingly high rate of incidence of the disease in the Kingdom as compared to the West. […] The estimated incidence of this condition is 7 in 100,000 live births.

• #22 Exploring molecular spectrum in thai patients with maple syrup urine disease: unveiling a common variant | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03411-7

  In Thailand, the incidence of MSUD remains undetermined. Expanded newborn screening, including MSUD, was initiated in October 2022. Prior to this, most of the patients were diagnosed based on the presence of clinical symptoms. Limited literature, comprising four scientific publications detailing 17 Thai MSUD patients have been reported without an exploration of genetic spectrum. […] This study is the first to describe the clinical and molecular spectrum of Thai MSUD patients before the implementation of expanded NBS. The 11-kb deletion involving exon 1 in the BCKDHB emerges as the most common variant among Thai individuals with MSUD. Furthermore, the gap-PCR test for detecting the 11-kb exon 1 deletion status holds the potential for integration into stepwise molecular analysis following positive expanded newborn screening.

• #23 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

  MSUD is one of the earliest and most important inborn errors included in metabolic newborn screening programs all over the world. […] In Egypt, we suffer a great lack of awareness of general practitioners concerning inherited disorders of inborn errors of metabolism especially in rural areas. […] Furthermore, the lack of a newborn screening program for inherited metabolic disorders leads to the delay in diagnosis and the development of severe and irreversible complications that result in handicapped children and sometimes fatality before diagnosis. […] We conducted this study to raise the awareness of health care physicians about MSUD by highlighting possible preliminary screening and diagnostic strategies. […] Moreover, identifying the underlying genetic background of MSUD is essential for proper genetic counseling and prenatal diagnosis to minimize the incidence of the disease.

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

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

  Historically, MSUD has had a worldwide incidence, occurring in one in 185,000 live births, but is much more frequent in certain founder populations including the Old Order Mennonites of Pennsylvania, where it may be observed in as many as one in every 200 live births. […] Since MSUD is amenable to treatment through dietary restriction of BCAAs (or treatment with thiamine in the responsive forms) and outcomes are generally very good if it is detected and treated within the first few days of life, routine NBS for the disorder is recommended. MSUD screening is currently incorporated in NBS programs throughout the United States, five Canadian provinces, 22 European countries, two Latin American countries (Costa Rica and Uruguay), and eight countries in the Asia Pacific region. […] NBS for MSUD has been performed since 1964 when the bacterial inhibition assay for leucine on dried blood spots (Guthrie specimen) was introduced. Today, NBS for inborn errors of BCAA metabolism typically involves quantitative plasma amino acid profiling by MS/MS.

• #25 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. […] Newborn screening programs in all 50 states include amino acid profiles which quantify the combined concentration of leucine, isoleucine, hydroxyproline, and alloisoleucine. 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. […] Early diagnosis and intervention are associated with better outcomes in MSUD. Consequently, the disorder is included in newborn screening panels in the United States.

• #26 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. […] MSUD has an estimated incidence between one in 100,000 to one in 300,000 births. […] 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.

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

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

  Maple syrup urine disease (MSUD) is a rare genetic disorder caused by the deficiency or inactivity of a specific enzyme responsible for metabolizing branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine. […] Newborn screening for MSUD is crucial for early diagnosis and management, as timely intervention can significantly improve outcomes. […] The disease is more prevalent in certain populations, such as Mennonites, highlighting the importance of genetic awareness and carrier testing in affected communities. […] MSUD affects about 1 in 185,000 newborns in the United States, but in some populations, such as Mennonites, it may be as high as 1 in 176. […] Some hospitals test for the disease in their newborn screening programs. Testing should be done within the first twenty-four hours after birth, since early diagnosis is essential. […] Carrier testing is available for the Mennonite variant of the disease.

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

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

  The milder variant forms of MSUD are often missed by NBS due to normal leucine levels in the newborn period. Individuals with mild forms may have greater residual enzyme activities and they typically appear after the neonatal period, usually before the second year of life. […] 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.

• #29 Maple syrup urine disease (MSUD)

  https://www.health.wa.gov.au/Articles/U_Z/WA-Newborn-Bloodspot-Screening-Program/Conditions-screened-for-in-WA/MSUD

  Approximately 1 in 100,000 births […] Mild forms of MSUD may be missed as the branched-chain amino acids may not be increased in the first weeks of life.

• #30

  https://www.jci.org/articles/view/67217

  Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances. […] Psychiatric illness is a reported MSUD complication, but has not been well characterized and remains poorly understood. […] Compared with 26 age-matched controls, MSUD patients were at higher risk for disorders of cognition, attention, and mood. […] Neuropsychiatric morbidity and neurochemistry were similar among transplanted and nontransplanted MSUD patients. […] In conclusion, amino acid dysregulation results in aberrant neural networks with neurochemical deficiencies that persist after transplant and correlate with neuropsychiatric morbidities. […] Despite important clinical progress, MSUD patients still have a high risk of neuropsychiatric disease that is not abrogated by liver transplant.

• #31

  https://www.jci.org/articles/view/67217

  Our results suggest that an asymptomatic newborn period, stringent leucine homeostasis, and cerebral essential amino acid (particularly valine) sufficiency are vital to long-term mental health and global function. […] The relationship of mood instability to early brain growth is particularly striking; patients diagnosed as encephalopathic newborns were 5 and 10 times more likely to later develop anxiety and depression, respectively, than those who remained metabolically stable throughout the neonatal transition. […] Chronic neurochemical deficiencies and correlations of metabolic control and neurochemistry with neuropsychiatric outcomes provide insight into basic physiological mechanisms that may underlie chronic MSUD brain disease.

• #32 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

  MSUD is one of the earliest and most important inborn errors included in metabolic newborn screening programs all over the world. […] In Egypt, we suffer a great lack of awareness of general practitioners concerning inherited disorders of inborn errors of metabolism especially in rural areas. […] Furthermore, the lack of a newborn screening program for inherited metabolic disorders leads to the delay in diagnosis and the development of severe and irreversible complications that result in handicapped children and sometimes fatality before diagnosis. […] We conducted this study to raise the awareness of health care physicians about MSUD by highlighting possible preliminary screening and diagnostic strategies. […] Moreover, identifying the underlying genetic background of MSUD is essential for proper genetic counseling and prenatal diagnosis to minimize the incidence of the disease.

• #33 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

  Recently the presidential health-care initiative that started in 2021 to screen diseased newborns and infants in governmental ICUs allover Egypt for metabolic disorders will provide an initial step to identify and manage such inherited diseases at earlier stages. […] The clinical outcome of MSUD is usually remarkable if it is detected early either through routine newborn screening or prenatally in affected families. […] Thus, highlighting the need for the regular implementation of newborn screening program by tandem mass spectrometry to detect presymptomatic cases, which will give a better chance for early specific management for MSUD affected newborns avoiding a potentially fatal outcome and improving their motor and mental development. […] Therefore, patient II/3, the sister of proband (II/2) was picked up and diagnosed at the age of 3 days before symptomatizing and standard MSUD formula was started earlier with close follow up.

• #34 Maple syrup urine disease – Wikipedia

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

  MSUD is a historically rare metabolic disorder with a worldwide incidence rate of about one in 185,000 live births. However, certain founder populations are much more prone to MSUD. For example, the Old Order Mennonites of Pennsylvania, produce as many as one in 200 live birth with MSUD. […] Maple syrup urine disease is classified as an autosomal recessive disorder and has a higher prevalence in populations that have higher consanguinity. Infants who are not treated for early onset MSUD experience a significant delay in development and usually die within a few months of birth. Younger children with late-onset MSUD may experience developmental delay also, depending on the enzyme activity of BKCD (branched-chain alpha-keto acid dehydrogenase). In children with periods of increased protein catabolism, there is an increased risk for metabolic decompensation. Early diagnosis can prevent morbidity in most cases as long as correct treatment is administered at presentation and periods of possible metabolic decompensation. MSUD occurs in all ethnic groups and the sex of the infant/child does not play a role in prevalence. […] NBS (newborn screening) programs incorporate MSUD screening in the United States, five provinces in Canada, Twenty-two European countries, eight Asian Pacific countries, and two Latin American countries.

• #35 Maple syrup urine disease

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

  Maple syrup urine disease (MSUD) is a rare but serious inherited condition. […] At around 5 days old, babies are offered newborn blood spot screening to check for inherited conditions like MSUD. […] If your child has MSUD, your clinical team will pass information about him or her on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

• #36 Orphanet: Maple syrup urine disease

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

  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.

• #37 Rare disease spotlight: Maple Syrup Urine Disease (MSUD)

  https://pentechealth.com/newsroom/rare-disease-spotlight-maple-syrup-urine-disease-msud/

  Maple Syrup Urine Disease (MSUD) affects approximately 1 in 185,000 newborns worldwide. […] MSUD is tested for through newborn screening programs, it is then diagnosed through additional blood and urine tests, ESI-Time of Flight mass spectrometry, and genetic studies of the patient. […] In families that have a history of MSUD prenatal testing may be done through either amniocentesis or chorionic villus biopsy to identify the disorder before birth, allowing clinicians to prepare early interventions as required.

• #38 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. […] 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.

• #39 Maple Syrup Urine Disease (MSUD) | New York State Department of Health, Wadsworth Center

  https://www.wadsworth.org/public-health-programs/newborn-screening/newborn-screening-program/maple-syrup-urine-disease-msud

  MSUD is very rare. It occurs in less than 1 in 185,000 newborns. It is more common in the Amish and Mennonite populations. […] Screening for MSUD is accomplished by measuring leucine by tandem mass spectrometry (MS/MS). […] Patients with an abnormal newborn screen for MSUD are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MSU.

• #40 Orphanet: Classic maple syrup urine disease

  https://www.orpha.net/en/disease/detail/268145

  Classic maple syrup urine disease (classic MSUD) is the most severe and probably common form of MSUD characterized by a maple syrup odor in the cerumen at birth, poor feeding, lethargy and focal dystonia, followed by progressive encephalopathy and central respiratory failure if untreated. […] Birth prevalence of MSUD is estimated at around 1/150,000. Classic MSUD may account for 50-75% of cases. […] Classic MSUD in neonates is a medical emergency.

• #41 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

  However, starting treatment during the first week of life is the strongest factor. […] In conclusion, 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. […] We further highlighted a patient with a rare complication of MSUD treatment leading to severe dermatological features of acrodermatitis dysmetabolica. […] In our study, we didn’t observe a clear phenotype-genotype correlation in our patients as the majority had a severe phenotype; however, early and aggressive intervention with specific treatment in the first few days of life resulted in normal development and a reasonable chance of a healthy productive life style as the second affected sibling in family II in our study, thus similar to other nations a newborn screening program for MSUD is crucial especially that Egypt has high rates of consanguineous marriages paving the way for a higher incidence of recessive genetic disorders.

• #42

  https://link.springer.com/article/10.1007/s44337-024-00041-7

  Currently, MSUD-specific infant formulas have been incorporated into the national formulary in Indonesia. […] This case report underscores the importance of considering inborn metabolism errors in infants with atypical clinical presentations. […] It emphasises the critical role of providing MSUD-specific formulas and understanding alternative dietary strategies to support optimal growth and development in MSUD patients.

• #43

  https://link.springer.com/article/10.1007/s44337-024-00041-7

  Maple syrup urine disease (MSUD) is a rare autosomal recessive inborn error of metabolism characterised by the impaired breakdown of branched-chain amino acids. […] Detecting MSUD in newborns is challenging due to the lack of distinctive signs, especially in resource-limited settings like Indonesia. […] The prevalence of MSUD is approximately 1 in 150,000 births. […] In 2014, Frazier and colleagues formulated evidence-based nutrition management guidelines for MSUD, recommending daily dietary BCAA and protein intake based on age groups. […] Various international formula milk producers offer MSUD-specific infant formula available in Indonesia upon request. […] However, the high cost and lack of national health insurance coverage for these formulas poses challenges for caregivers, necessitating a comprehensive understanding of the disease and available nutritional alternatives.

• #44 Gene therapy developed for maple syrup urine disease shows promise, new UMass Chan study reports

  https://www.umassmed.edu/news/news-archives/2025/02/gene-therapy-developed-for-maple-syrup-urine-disease-shows-promise-new-umass-chan-study-reports/

  A study led by UMass Chan Medical School researchers demonstrated that a gene therapy to correct a mutation that causes maple syrup urine disease (MSUD) prevented newborn death, normalized growth, restored coordinated expression of the affected genes and stabilized biomarkers in a calf as well as in mice. […] MSUD is a rare genetic inborn error of metabolism characterized by recurrent life-threatening neurologic crises and progressive brain injury that can only be managed with an exacting prescription diet or liver transplant from a donor. […] The condition occurs in one in 197,714 live births but is much more common in certain regions of Brazil, Portugal, Turkey, the Philippines, and among people of Ashkenazi or Mennonite descent. Among the Mennonite population such as communities in Lancaster County, Pennsylvania, the incidence of MSUD is one in 400.

• #45 Gene therapy developed for maple syrup urine disease shows promise, new UMass Chan study reports

  https://www.umassmed.edu/news/news-archives/2025/02/gene-therapy-developed-for-maple-syrup-urine-disease-shows-promise-new-umass-chan-study-reports/

  Researchers in the current study designed a dual-function recombinant adeno-associated virus serotype 9 vector to deliver a gene replacement to the liver, muscle, heart and brain. […] Wang said that researchers are exploring with the U.S. Food and Drug Administration the next steps to translate this gene therapy into clinical use as a Phase I/II study.

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