Presentation
[…] 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]
Clinical presentation is similar to those with intermediate MSUD, but severe lactic acidosis is also present. [motherbabyuniversity.com]
Older children usually present with learning difficulties. [orpha.net]
Entire Body System
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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]
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Epilepsy
E-2018 115 Viral Infections of the Nervous System E-2041 116 Fungal Rickettsial and Parasitic Diseases of the Nervous System E-2075 117 Neurologic Complications of Immunization E-2132 118 Paraneoplastic Neurologic Syndromes E-2142 119 ImmuneMediated Epilepsy [books.google.de]
Gastrointestinal
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Abdominal Pain
Some symptoms of inherited metabolic disorders include: Lethargy Poor appetite Abdominal pain Vomiting Weight loss Jaundice Failure to gain weight or grow Developmental delay Seizures Coma Abnormal odor of urine, breath, sweat, or saliva The symptoms [webmd.com]
Workup
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]
Treatment
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]
There are 2 aspects of treatment: long-term management and treatment during acute metabolic crisis. [wvdhhr.org]
Management and treatment Treatment of intermediate MSUD is similar to classic MSUD. Infants require high calorie BCAA-free formulas, dietary leucine restriction and close outpatient monitoring at a metabolic clinic. [orpha.net]
Prognosis
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]
[…] decorticate rigidity Lab BCAA, threonine, serine, alanine in urine and serum, a positive dinitro-phenylhydrazine test for α keto amino acids, which form insoluble hydrazines Treatment Dietary 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
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]
Epidemiology
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]
Pathophysiology
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]
Prevention
• Novel therapies investigated include hepatocyte transplantation, drugs to counter oxidative stress, norleucine, and phenylbutyrate to prevent the inactivation of the dehydrogenase complex. [medlink.com]
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]
Identifying the presence of MSUD at birth is critical to preventing long-term damage. [healthline.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]
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]