[…] ranges from a severe neonatal presentation with neurological deficits to a less severe childhood presentation with exertional fatigue between decompensation episodes. Patients may also present with severe liver failure. [quizlet.com]

May present with feeding problems, poor growth and developmental delay during infancy, or may present much later in life with learning difficulties. Usually diagnosed between ages 5 months and 7 years. [patient.info]

Overview Maple syrup urine disease is an inborn error of branched-chain ketoacid metabolism that presents classically with metabolic distress in newborns, although milder presentations exist. [medlink.com]

Clinical presentation is similar to those with intermediate MSUD, but severe lactic acidosis is also present. [motherbabyuniversity.com]

Screening Presentations Classic form of MSUD Presentation is in the neonatal period, although children usually do not become symptomatic in the first few days of life while leucine accumulates in the brain. [medicalhomeportal.org]

• Weight Loss

  Some of the initial symptoms of classic MSUD include irregular sleep patterns, lethargy, irritability, weight loss, poor appetite, and a distinctive maple sugar odor in earwax, sweat, and urine (which gives the disorder its name). [medicaldaily.com]

  With the progression of the disease, further signs include weight loss and progressive neurological deterioration. [maplesyrupstory.blogspot.com]

  With progress of the disease it comes to weight loss and progressive neurological deterioration and hypo- to hypertonia. If the disease is not treated it leads to coma and death within several months after birth. [i12r-studfilesrv.informatik.tu-muenchen.de]

  Within several days, the infant will show poor feeding, vomiting, and irritability, followed by lack of energy, weight loss, seizures, a tense arched posture, muscle tone which alternates between stiff and limp, and swelling of the brain. [counsyl.com]

  Some common symptoms of classic MSUD are: Extreme fatigue, irritability and lethargy High pitched cry Poor feeding, loss of appetite and weight loss Irregular sleep rhythm Poor suckling Alternating episodes of hypotonia (flaccidity of muscles) and hypertonia [drelist.com]

• Disability

  If symptoms appear prior to the initiation of treatment, the chance of developmental disability is high. [motherbabyuniversity.com]

  These may create learning problems or mental disability and can be life-threatening. If untreated, MSUD can be fatal. [counsyl.com]

  Preventing intellectual disability A decrease in IQ over the years may be avoidable by strict adherence to dietary restrictions and avoidance of decompensation due to stress. [medicalhomeportal.org]

  If your infant is diagnosed with MSUD, prompt medical treatment can avoid serious medical problems and intellectual disability. Initial treatment involves reducing the levels of BCAAs in your baby’s blood. [healthline.com]

  Disabled World. Retrieved 2016-11-10. ^ Jaworski MA, Severini A, Mansour G, Konrad HM, Slater J, Henning K, Schlaut J, Yoon JW, Pak CY, Maclaren N, et al. (1989). [en.wikipedia.org]

• Crying

  Other important syptoms are poor feeding, poor appetite, weak suck, lethargy, high pitched cry, and movements that look like fencing or bicycling. [maplesyrupurine.weebly.com]

  Some common symptoms of classic MSUD are: Extreme fatigue, irritability and lethargy High pitched cry Poor feeding, loss of appetite and weight loss Irregular sleep rhythm Poor suckling Alternating episodes of hypotonia (flaccidity of muscles) and hypertonia [drelist.com]

  Clinical presentation of classic MSUD includes - Poor sucking with little interest in feeding Marked lethargy Weight loss Vomiting Rapid shallow respirations High-pitched cry Hypotonia alternating with periods of hypertonicity Dystonic posturing of the [motherbabyuniversity.com]

  […] lethargy poor appetite weight loss weak sucking ability irritability a distinctive maple sugar odor in earwax, sweat, and urine irregular sleep patterns alternating episodes of hypertonia (muscle rigidity) and hypotonia (muscle limpness) high-pitched cry [healthline.com]

  Affected infants are poor feeders, irritable, lethargic, have irregular sleep patterns and a high-pitched cry. They can suffer from spasms, where the head, neck and spine arch backwards, involuntary muscle contractions and an abnormal posture. [jewishdiseasedna.com]

• Asymptomatic

  Initially, these children will be asymptomatic and thus show normal early development with normal intellectual levels. During this period of time, the BCAA levels will remain normal. [maplesyrupstory.blogspot.com]

  During periods when patients are asymptomatic their fluid levels of BCAAs will be normal. These patients are however, at risk for acute metabolic decompensation during periods of stress. [themedicalbiochemistrypage.org]

  Treatment Treatment of MSUD is divided into acute (symptomatic) stage treatment and chronic (asymptomatic) stage treatment ( 32, 33 ). Acute stage treatment. Early diagnosis and early treatment is the principle for acute stage treatment. [jn.nutrition.org]

  […] of presentations of MSUD include the classic (most severe and most common form at risk for major metabolic crisis in newborn and later periods), intermediate (elevations in metabolites with little or no risk for metabolic crisis), and intermittent (asymptomatic [newenglandconsortium.org]

  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 [emedicine.medscape.com]

• Pathologist

  Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication [invitae.com]

• Flatulence

  In Egypt, Helba tea is commonly used to reduce flatulence and prevent fever. This tea includes seeds of fenugreek that contains sotolone, the compound responsible for the aroma in maple syrup urine disease. [cags.org.ae]

• Seizure

  The condition can then lead to progressive degeneration of brain functions, seizures, coma and death, especially when left untreated. [healthfoxx.com]

  Clinical features were characterized by mental retardation, seizures, autistic features, and movement disorder in the form of dystonia. [ncbi.nlm.nih.gov]

  Long-term sequelae may include developmental delays, learning problems, seizures and motor difficulties. Even with dietary treatment, stressful situations and illness can still cause high levels of certain amino acids. [secure.ssa.gov]

  If untreated, it may lead to seizures, coma, and death. [icd10data.com]

  Elevated levels can lead to brain injury, mental retardation, seizures, coma and even death. [motherbabyuniversity.com]

• Lethargy

  Neurological signs and symptoms such as lethargy, seizures, ataxia, are present. E3-deficient MSUD This type is a very rare form of Maple Syrup Urine Disease. [healthfoxx.com]

  Metabolic crisis manifests as extreme sleepiness, lethargy, irritable mood, and vomiting. If not treated, seizures, coma and even death can occur. [maplesyrupurine.weebly.com]

  It is also characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development. [ncbi.nlm.nih.gov]

  The children seem normal at birth but after 4 to 7 days after birth the first symptoms like lethargy and little interest in feeding appear. [i12r-studfilesrv.informatik.tu-muenchen.de]

  For example, high intake of branched-chain amino-acids can lead to irritability, seizures, lethargy, loss of mental alertness and vomiting. [drelist.com]

• Dystonia

  Clinical features were characterized by mental retardation, seizures, autistic features, and movement disorder in the form of dystonia. [ncbi.nlm.nih.gov]

  Like classic MSUD (see this term), catabolic stress can result in acute decompensation with anorexia, vomiting, ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute dystonia, choreoathetosis [orpha.net]

  Early signs and symptoms are poor feeding, vomiting, lethargy, hypo or hypertonia, dystonia, seizures and encephalopathy which can lead to early death or permanent neurologic damage. Later in infancy or childhood, developmental delays are noted. [secure.ssa.gov]

• Hyperactivity

  Like classic MSUD (see this term), catabolic stress can result in acute decompensation with anorexia, vomiting, ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute dystonia, choreoathetosis [orpha.net]

  If untreated, it progresses to irreversible mental retardation, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death. [mayomedicallaboratories.com]

  Adolescents and adults with MSUD are at increased risk for attention deficit hyperactivity disorder (ADHD), depression and anxiety disorders. [ 2 ] Non-central nervous system involvement in MSUD can include: [ 2 ] Nutritional deficiencies: Chronic deficiency [patient.info]

  His Moro's reflex was hyperactive and eyes were not fixing to the light. His urine also smelled sweet, and based on his brother's history, he was diagnosed with MSUD, and put on MSUD Aid with thiamine, beginning on the 19th post natal day. [cags.org.ae]

• Convulsions

  The baby's condition worsened over time and at 3-weeks of age, he developed focal convulsions, and died at 37-days of age. [cags.org.ae]

  Coitinho-AS; de-Mello-CF; Lima-TTF; de-Bastiani-J; Fighera-MR; Wajner-M Pharmacological evidence that alpha-ketoisovaleric acid induces convulsions through GABAergic and glutamatergic mechanisms in rats Brain-Research. [malattierare.regione.veneto.it]

  […] branched chain amino acids–BCAA, valine, leucine and isoleucine results in accumulation of BCAA Clinical Neonatal onset, ↓ Moro reflex, dyspnea, spasticity, opisthotonos, mental and growth retardation, severe hypotonia, feeding difficulties, hypoglycemia, convulsions [medical-dictionary.thefreedictionary.com]

  Other symptoms, such as unconsciousness, convulsion, opisthotonus, and apnea, apparently occurred with blood levels of leucine over 1000 μmol/L ( Fig. 2 ). [jn.nutrition.org]

• Phenylketonuria

  Phenylketonuria (PKU): Deficiency of the enzyme PAH results in high levels of phenylalanine in the blood. Mental retardation results if the condition is not recognized. [webmd.com]

  Thirty-five patients with aminoacidopathy were identified, all but two of whom were the offspring of first-degree consanguineous marriages: nine cases of phenylketonuria, one benign hyperphenylalaninemia, seven non-ketotic hyperglycinemia, five tyrosinemia [cags.org.ae]

  Website: Cambrooke Foods is a supplier of low-protein foods for people with phenylketonuria and MSUD; it is also a distributor of Vitaflo products within the United States. Clinic for Special Children. 535 Bunker Hill Road, Stras-burg, PA 17579. [diet.com]

  Phenylketonuria Scientific Review Conference: State of the science and future research needs. Mol Genet Metab. 2014;112(2):87-122. Chin HL, Aw MM, Quak SH, et al. [acertx.com]

Only samples with both increased total leucine and increased alloisoleucine would lead to further metabolic workup. This approach appears promising for further reducing false-positive rates. [clinchem.aaccjnls.org]

Biochemical workup MSUD in a newborn may be suspected due to the presence of illness and/or an abnormal neonatal screening test result. [dovepress.com]

• Ketonuria

  […] mL) | Buccal Swabs Billing ICD Codes: 796.6 Abnormal findings on neonatal screening 270.3 Disturbances of branched-chain amino-acid metabolism, Disturbances of metabolism of leucine, isoleucine, and valine, Hypervalinemia Intermittent branched-chain ketonuria [genedx.com]

  • Soon after birth, maple syrup urine disease classically presents with an encephalopathy accompanied by abnormal movements such as pedaling, ketonuria, and urine with a burnt sugar odor. • The metabolic defect is in the branched-chain keto acid dehydrogenase [medlink.com]

  […] standard urine test strips; ketonuria in a newborn should always be followed by investigation for metabolic disorders. [ 2 ] Plasma amino acids: elevation of BCAAs. [patient.info]

  The spillage of poorly degraded amino acids imparts a distinct smell to the urine; thereby leading to maple syrup urine disease (also known as branched-chain ketonuria I or branched-chain ketoaciduria ). [drelist.com]

  MSUD is also known as: BCKDC deficiency branched-chain alpha-keto acid dehydrogenase deficiency branched-chain ketoaciduria branched-chain ketonuria I There are four subtypes of MSUD. All are inherited genetic disorders. [healthline.com]

• Hypoglycemia

  ICD Codes: 796.6 Abnormal findings on neonatal screening 270.3 Disturbances of branched-chain amino-acid metabolism, Disturbances of metabolism of leucine, isoleucine, and valine, Hypervalinemia Intermittent branched-chain ketonuria, Leucine-induced hypoglycemia [genedx.com]

  The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. [icd10data.com]

  Lifelong considerations Children with MSUD will have a lifelong risk for episodes of ketoacidosis, and hypoglycemia. A child with MSUD should be monitored closely for growth and development. [maplesyrupurine.weebly.com]

  […] decarboxylation of branched chain amino acids–BCAA, valine, leucine and isoleucine results in accumulation of BCAA Clinical Neonatal onset, ↓ Moro reflex, dyspnea, spasticity, opisthotonos, mental and growth retardation, severe hypotonia, feeding difficulties, hypoglycemia [medical-dictionary.thefreedictionary.com]

ACER-001 was granted orphan drug designation as a potential treatment for MSUD in 2014. [acertx.com]

TREATMENT When the condition is diagnosed and during episodes, treatment involves eating a protein-free diet and correction of the metabolic consequences of the elevated amino acid levels. [secure.ssa.gov]

Treatment during these episodes focuses on emergency care and improving organ function. [webmd.com]

There are 2 aspects of treatment: long-term management and treatment during acute metabolic crisis. [wvdhhr.org]

If your infant is diagnosed with MSUD, prompt medical treatment can avoid serious medical problems and intellectual disability. Initial treatment involves reducing the levels of BCAAs in your baby’s blood. [healthline.com]

Prognosis With early diagnosis and appropriate therapy the prognosis is good, but because the disorder is mild, diagnostic delay is common and some neurological damage may be sustained. [orpha.net]

Increased BCAA, decreased threonine, serine, alanine in urine and serum, positive dinitro-phenylhydrazine test for alpha-keto amino acids, which form insoluble hydrazines Management Dietary decrease of BCAA, plus dietary overload—20-fold excess of thiamine Prognosis [medical-dictionary.thefreedictionary.com]

12 Prognosis Overall very poor if left undetected/untreated With treatment and proper dietary management, the prognosis is good However, severe stress and illness can cause a surge of certain amino acids 13 Medical Management of MSUD Long-term management [slideplayer.com]

The prognosis of such untreated infants is poor with death occurring within the first few months of birth due to complications of metabolic crisis and neurological deterioration. 2) Intermediate The Intermediate MSUD is a variant form of the classic MSUD [maplesyrupstory.blogspot.com]

Etiology MSUD is due to mutations in genes encoding 3 of the 4 subunits of the branched chain 2-ketoacid dehydrogenase (BCKAD) complex. [orpha.net]

Oltarzewski-M; Lenartowska-I Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience Med-Wieku-Rozwoj. 1999 Oct-Dec; 3(4): 529-59 Lebo-RV; Shapiro-LR; Fenerci-EY; Hoover-JM; Chuang-JL; Chuang-DT; Kronn-DF Rare etiology [malattierare.regione.veneto.it]

Summary Epidemiology The estimated birth prevalence of MSUD is 1/ 150,000. Around 30% of cases are believed to be of the intermediate type. [orpha.net]

Genatlas disease for DBT Gene maple syrup urine disease Relevant External Links for DBT Genetic Association Database (GAD) DBT Human Genome Epidemiology (HuGE) Navigator DBT Atlas of Genetics and Cytogenetics in Oncology and Haematology: DBT The complete [genecards.org]

Molecular genetic testing of all three genes is available. [ 2 ] Epidemiology [ 1 ] Worldwide, MSUD occurs in about 1 case per 185,000 live births. [patient.info]

The accumulation of plasma isoleucine is associated with the maple syrup urine odor. [10, 11] Epidemiology Frequency United States Maple syrup urine disease occurs in about 1 case per 185,000 live births. [emedicine.medscape.com]

Useful For Suggests clinical disorders or settings where the test may be helpful Follow-up of patients with maple syrup urine disease Monitoring of dietary compliance for patients with maple syrup urine disease Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]

The pathophysiology of MSUD revolves around relative deficiency or absolute lack of enzyme that are collectively referred to as branched-chain alpha-ketoacid dehydrogenase complex (or BCKAD). [drelist.com]

Pathophysiology Catabolic stress such as normal perinatal catabolism or an acute illness (e.g. infection, injury, surgery, febrile illness) produces endogenous protein breakdown leading to increase in the BCAA and related branched chain ketoacids. [newenglandconsortium.org]

[…] of branched-chain amino acids. [4] In 1971, Scriver et al reported the first case of thiamine-responsive maple syrup urine disease. [5] The branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex was purified and characterized in 1978. [2] Pathophysiology [emedicine.medscape.com]

Various combinations of dietary therapy, vitamin therapy (thiamine and biotin), and lipoic acid have been tried without success. 122 Pathophysiology The BCKD complex is a macromolecule composed of 3 catalytic components: a thiamine pyrophosphate–dependent [wvdhhr.org]

XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004: 27(1):155-161. ‎ [books.google.es]

• Novel therapies investigated include hepatocyte transplantation, drugs to counter oxidative stress, norleucine, and phenylbutyrate to prevent the inactivation of the dehydrogenase complex. [medlink.com]

Identifying the presence of MSUD at birth is critical to preventing long-term damage. [healthline.com]

The boy from High Ridge had received high priority because he had a rare condition, maple syrup urine disease, which prevented his body from properly processing protein. [mbc-cythl.blogspot.com]

Instead, the newborn’s urine is analyzed for levels of branched-chain alpha-hydroxyacids and alpha-ketoacids. [6] Prevention [ edit ] There are no methods for preventing the manifestation of the pathology of MSUD in infants with two defective copies of [en.wikipedia.org]