Materiały źródłowe

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

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

  Maple syrup urine disease (MSUD) is a defect of amino acid metabolism due to abnormal activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex. This complex is responsible for breaking down the 3 essential branched-chain amino acids (BCAA): isoleucine, leucine, and valine. […] MSUD occurs when an underlying defect in the BCKAD complex located in the cellular mitochondria disrupts the metabolism of BCAA, which leads to their accumulation in the plasma, brain, and other tissues as well as their respective derivative ketoacids in the urine. […] MSUD occurs due to a pathogenic defect in any BCKAD subunit, resulting in elevated branched-chain amino acids and their corresponding alpha keto-acids. Accumulated BCAA and alpha-ketoacids manifest as a constellation of clinical symptoms due to the central nervous system, immune system, and skeletal muscle dysfunction.

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

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

  Elevated leucine and alpha-ketoisocaproic acid levels notoriously cause neurochemical disturbances, resulting in clinically apparent neurotoxicity. Neurotoxicity is aggravated by the metabolic decompensation in MSUD, which activates matrix metalloproteinases, resulting in the further breakdown and dysfunction of the blood-brain barrier. […] High intracranial leucine concentrations compete with the cerebral uptake of several other important amino acids, particularly phenylalanine, glutamine, histidine, methionine, and tryptophan, negatively impacting brain growth, neurotransmitter production, and myelin synthesis. […] The restricted supply of essential amino acids leads to decreased neurotransmitters, including dopamine, serotonin, norepinephrine, epinephrine, GABA, and glutamate. […] Experts theorize that the citric acid cycle in the brain is destroyed by BCAA inhibition of pyruvate and -ketoglutarate dehydrogenase, as well as the mitochondrial respiration chain, which affects amino acid and protein synthesis, causing abnormal myelination and cerebral edema. […] Long-term exposure to high levels of BCAA will cause myelin dysplasia.

• #2 Maple syrup urine disease: mechanisms and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5593394/

  Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain -ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino acids (BCAAs) in plasma, -ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine. […] MSUD is a metabolic disorder caused by decreased function of the BCKAD enzyme complex. Biallelic pathogenic variants in the catalytic components of BCKAD decrease its activity thereby increasing BCAA levels and causing toxicity within skeletal muscle and brain tissue. […] During the second step in BCAA catabolism, the BCKAD complex initiates oxidative decarboxylation of -ketoacids. This process results in the conversion of -ketoacids into acetoacetate, acetyl-CoA, and succinyl-CoA as illustrated in Figure 1. The BCKAD complex is made up of several components, including subunits E1 and E1, E2, and E3. Increased BCAA levels within the body due to pathogenic defects in these components cause MSUD, leading to a variety of symptoms mentioned above, including dysfunction of the immune system, skeletal muscle, and central nervous system (CNS).

• #2 Maple syrup urine disease: mechanisms and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5593394/

  Elevated levels of leucine can affect water homeostasis within the subcortical gray matter causing swelling within the brain, alter nitrogen homeostasis further depleting glutamate levels, increase oxidative stress, and compete with other important amino acids within the CNS such as tyrosine, which is involved in protein signaling. In addition, there is evidence that -ketoisocaproic acid, an intermediate in the metabolism of leucine, is a major neuro-toxin contributing to the encephalopathic syndrome. […] Although the specific outcomes of BCAA abnormalities have not been fully characterized, it is apparent that proper metabolism is critical for human health.

• #3 Overview of maple syrup urine disease – UpToDate

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

  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. […] MSUD is caused by pathogenic variants of genes that encode branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) components E1-alpha, E1-beta, E2, and E3. These genes map to human chromosomes 19q13.1-q13.2 (BCKDHA), 6p22-p21 (BCKDHB), 1p31 (dihydrolipoamide branched-chain transacylase E2 [DBT]), and 7q31-q32 (dihydrolipoamide dehydrogenase [DLD]), respectively. The mode of inheritance is autosomal recessive. The sequences of all genes are fully characterized, including regulatory elements. Homozygous or compound heterozygous variants in any of these genes can cause any of the forms of MSUD.

• #3 Overview of maple syrup urine disease – UpToDate

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

  BCKDC plays a key role in the metabolism of BCAAs for energy production and synthesis of fatty acids and cholesterol through gluconeogenesis. Decreased activity of BCKDC results in elevation of plasma concentrations of the BCAAs (leucine, isoleucine, and valine) and their corresponding keto acids. A metabolite of isoleucine causes the urine to smell like maple syrup. Elevated levels of BCAA interfere with normal function of the immune system, skeletal muscle, and central nervous system, exerting direct and indirect neurotoxic effects through tissue swelling, impaired glutamate homeostasis, and relative deficiency of large neutral amino acids, resulting in reduced neurotransmitter synthesis including dopamine and serotonin.

• #4 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 is caused by pathogenic variants of genes that encode branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) components E1-alpha, E1-beta, E2, and E3. These genes map to human chromosomes 19q13.1-q13.2 (BCKDHA), 6p22-p21 (BCKDHB), 1p31 (dihydrolipoamide branched-chain transacylase E2 [DBT]), and 7q31-q32 (dihydrolipoamide dehydrogenase [DLD]), respectively. The mode of inheritance is autosomal recessive. The sequences of all genes are fully characterized, including regulatory elements. Homozygous or compound heterozygous variants in any of these genes can cause any of the forms of MSUD. No strict genotype-phenotype correlation exists in patients with MSUD. Founder variants are identified in populations with a particularly high prevalence of MSUD (eg, Mennonites, Amish).

• #4 Overview of maple syrup urine disease – UpToDate

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

  BCKDC plays a key role in the metabolism of BCAAs for energy production and synthesis of fatty acids and cholesterol through gluconeogenesis. Decreased activity of BCKDC results in elevation of plasma concentrations of the BCAAs (leucine, isoleucine, and valine) and their corresponding keto acids. A metabolite of isoleucine causes the urine to smell like maple syrup. Elevated levels of BCAA interfere with normal function of the immune system, skeletal muscle, and central nervous system, exerting direct and indirect neurotoxic effects through tissue swelling, impaired glutamate homeostasis, and relative deficiency of large neutral amino acids, resulting in reduced neurotransmitter synthesis including dopamine and serotonin.

• #5 Maple syrup urine disease – Genomics Education Programme

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

  Maple syrup urine disease (MSUD) is an autosomal recessive disorder that prevents the body from metabolising the branched-chain amino acids: leucine, isoleucine and valine. […] MSUD is an autosomal recessive disorder caused by decreased activity of the branched-chain alpha-ketoacid dehydrogenase complex (BCKAD). […] BCKAD is comprised of four subunits (E1a, E1b, E2 and E3), and is the enzyme responsible for the second step in the catabolic pathway for the branched-chain amino acids (leucine, isoleucine and valine). […] Variants in the genes that encode three out of the four subunits of BCKAD can cause MSUD. […] In classic MSUD variants in the BCKDHA gene, encoding the E1a subunit, predominate. Variants in the BCKDHB and DBT genes, which encode E1b and E2 respectively, are more common in the milder variant forms. […] The management of MSUD is centred upon avoiding the toxic accumulation of BCAAs. This is achieved by the restriction of dietary leucine and the careful manipulation of calorie intake to avoid catabolism.

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

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

  Maple syrup urine disease is caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex, which catalyses the decarboxylation of the alpha-keto acids of leucine, isoleucine, and valine to their respective branched-chain acyl-CoAs. These are further metabolized to yield acetyl-CoA, acetoacetate, and succinyl-CoA. […] The BCKD enzyme complex, which is associated with the inner mitochondrial membrane, has 3 different catalytic components (ie, E1, E2, E3) and 2 associated regulatory enzymes (ie, BCKD phosphatase, BCKD kinase). In addition, the E1 component consists of 2 distinct subunits (ie, E1 alpha, E1 beta) that form an alpha-2 beta-2 heterotetramer. […] Mutations in E1, E2, or E3 cause maple syrup urine disease. No clear genotype-phenotype correlation between molecular and clinical phenotypes is known, with the exemption of mutations in E2, which cause thiamine-responsive maple syrup urine disease. […] Accumulation of plasma leucine causes neurological symptoms. Leucine is rapidly transported across the blood-brain barrier and is metabolized to presumably yield glutamate and glutamine. The accumulation of plasma isoleucine is associated with the maple syrup urine odor.

• #7 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. […] The BCAA (ie, isoleucine, leucine, and valine) are essential amino acids with hydrophobic side chains in protein-rich food. The catabolism of these amino acids is necessary to maintain various physiologic functions, including: […] Elevated leucine and alpha-ketoisocaproic acid levels notoriously cause neurochemical disturbances, resulting in clinically apparent neurotoxicity. Neurotoxicity is aggravated by the metabolic decompensation in MSUD, which activates matrix metalloproteinases, resulting in the further breakdown and dysfunction of the blood-brain barrier. […] High intracranial leucine concentrations compete with the cerebral uptake of several other important amino acids, particularly phenylalanine, glutamine, histidine, methionine, and tryptophan, negatively impacting brain growth, neurotransmitter production, and myelin synthesis.

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

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

  The restricted supply of essential amino acids leads to decreased neurotransmitters, including dopamine, serotonin, norepinephrine, epinephrine, GABA, and glutamate. […] Alpha-ketoisocaproic acid levels greater than 60 mmol/L negatively affect astrocyte transamination reactions. […] This restriction causes low cerebral glutamate levels, which results in cognitive dysfunctions (eg, learning disabilities and memory loss). […] Furthermore, elevated leucine concentrations impair cell volume regulation. This results in decreased blood osmolarity, low sodium concentrations, and increased intracellular water, leading to cerebral edema. […] In infants and children, decreased blood osmolarity can exacerbate cerebral edema and further precipitate brain herniation. […] Experts theorize that the citric acid cycle in the brain is destroyed by BCAA inhibition of pyruvate and -ketoglutarate dehydrogenase, as well as the mitochondrial respiration chain, which affects amino acid and protein synthesis, causing abnormal myelination and cerebral edema. […] Long-term exposure to high levels of BCAA will cause myelin dysplasia.

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

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

  Elevated levels of leucine can affect water homeostasis within the subcortical gray matter causing swelling within the brain, alter nitrogen homeostasis further depleting glutamate levels, increase oxidative stress, and compete with other important amino acids within the CNS such as tyrosine, which is involved in protein signaling. In addition, there is evidence that -ketoisocaproic acid, an intermediate in the metabolism of leucine, is a major neurotoxin contributing to the encephalopathic syndrome. […] While genetic variants in certain components of this pathway lead to MSUD, several other disorders have been associated with abnormal BCAA metabolism, including insulin resistance and type 2 diabetes mellitus, liver disease, and certain types of cancer, broadening its respective roles in human health.

• #9 Maple syrup urine disease – Wikipedia

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

  Amino acid transport deficiency and neurotransmitter synthesis impairment are significant concerns in individuals with maple syrup urine disease. […] Increased plasma concentrations of branched-chain keto acids (BCKA) are transported through the blood–brain barrier via the monocarboxylate transporter (MCT/SLC16A1). Elevated levels of alpha-ketoisocaproate (α-KIC) result in a reduction in glutamate, glutamine, and GABA. […] Neurotoxic effects have been observed in experimental studies linking the accumulation of BCAA and BCKA to the neuropathology seen in individuals with MSUD.

• #10

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

  Hyperleucinemia inhibits the transport of tyrosine, tryptophan, and other essential amino acids across the blood-brain barrier and thereby limits substrate availability for cerebral catecholamine, serotonin, and protein synthesis. […] Elevated aKIC the ketoacid derivative of leucine reverses the net direction of nitrogen flow and thus depletes the brain of glutamate. […] Supporting the energy inhibition hypothesis, BCKDHA knockout mouse brain has low pyruvate, ATP, and phosphocreatine, and high -ketoglutarate, lactate, and alanine. […] Cerebral edema during acute crises consists of both a global vasogenic edema thought to be related to blood-brain barrier compromise and MSUD edema, which is thought to be intramyelinic, cytotoxic edema secondary to energetic and osmotic dysregulation.

• #10

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

  Neurotransmitter deficiencies can be a primary cause of psychiatric illness or entrain compensatory changes in receptor expression and synaptic structure that affect brain function. […] Cerebral myo-inositol, important in cell growth and osmoregulation, correlates with both intelligence and mood. […] The association of affective disorders with prefrontal and anterior cingulate neurochemical deficiencies supports the notion that these regions play a role in regulating emotions. […] Despite important clinical progress, MSUD patients still have a high risk of neuropsychiatric disease that is not abrogated by liver transplant.

• #11 Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

  https://www.mdpi.com/1422-0067/21/20/7490

  Recent studies have shown evidence of dysregulation of certain amino and organic acids in the CNS of MSUD patients, related to the disruption of BCAAs catabolism in these individuals. […] One proposed mechanism for the decrease in glutamate and elevation in lactate levels is that, in MSUD patients, the increased levels of BCKAs (specifically α-ketoisocaproic acid) leads to reversed flux through BCAT, which normally catalyzes the conversion of BCAAs and α-ketoglutarate to BCKAs and glutamate. […] Overall, the dysregulation of these AAs may lead to brain dysfunction, predisposing MSUD patients to cognitive and psychiatric disabilities despite major clinical interventions such as liver transplant. […] Studies of neurological symptoms in MSUD patients remain somewhat limited. Currently, available literature showed that, despite strict diet therapy or liver transplantation that restore peripheral BCAA homeostasis, MSUD patients are at higher risk for neuropsychological impairments including cognitive deficits and mental illness (anxiety, depression, ADHD, and OCD) compared to healthy controls. […] In summary, evidence suggests that abnormalities in aromatic AAs, the related monoamine neurotransmitters, methionine, and antioxidants cysteine and glutathione may contribute to BCAA-induced neurological symptoms in MSUD.

• #12 Maple Syrup Urine Disease (MSUD) — New England Consortium of Metabolic Programs

  https://www.newenglandconsortium.org/msud

  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. […] Increased concentrations of leucine are toxic to the brain and accumulations may result in cerebral edema. Caution should be exercised when considering the need for a lumbar puncture. […] Brain edema (with associated brain stem herniation) is the most frequent cause of death in MSUD.

• #13 ERIC – EJ843327 – Dual Mechanism of Brain Injury and Novel Treatment Strategy in Maple Syrup Urine Disease, Brain, 2009-Apr

  https://eric.ed.gov/?id=EJ843327

  Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with life-threatening cerebral oedema and dysmyelination in affected individuals. […] The mechanisms underlying this decompensation and brain injury are poorly understood. […] Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. […] Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branched-chain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. […] Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease.

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

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

  Maple syrup urine disease is due to mutations in any aspect of the mitochondrial branched-chain alpha-keto acid dehydrogenase complex. […] There is elevated plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine), allo-isoleucine, and alpha-ketoacids. […] MRI brain may show the characteristic pattern of edema present in MSUD. Two forms of edema may be seen in MSUD: intramyelinic edema: believed to be from myelin splitting due to accumulation of branched-chain key acids and water molecules between layers of myelin and vasogenic edema: usually due to disruption of the blood-brain barrier during an acute metabolic crisis or decompensation.

• #15

  https://journals.lww.com/md-journal/fulltext/2022/12160/neonatal_maple_syrup_urine_disease_case_report_and.6.aspx

  The brain MRI DWI findings of this patient with MSUD were consistent with the cytotoxicity or intramedullary edema reported in the previous literature rather than vascular or interstitial edema. The decrease in activity of Na+/K+ATPase causes an increase of the intracellular Na+ concentration. Diffuse brain edema and strong local edema occur with the liquid transfer to the cells, which also known as MSUD edema. […] The DWI and ADC show hyperintensity and hypointensity respectively. The DWI of brain edema is specific and symmetrical hyperintensity. It is caused by edema in the myelin sheath, limited diffusion of water molecules, and toxic intracellular edema. DWI is the optimal detection method for neonatal MSUD encephalopathy. […] Newborn MSUD is often a classic type with the most serious clinical symptoms. It is characterized by progressive seizures, high muscular tension, feeding difficulties and others, which would worse about 1 week after birth. […] In addition, liver transplantation is an effective treatment for it. This treatment can prevent potential new brain injury and promote neural development.

• #16 Branched-Chain Amino Acid Assembly into Amyloid-like Fibrils Provides a New Paradigm for Maple Syrup Urine Disease Pathology

  https://www.mdpi.com/1422-0067/24/21/15999

  Branched-chain amino acids (BCAAs) that accumulate in maple syrup urine disease (MSUD) can self-assemble into amyloid-like fibrils depicted by characteristic morphology, binding to indicative amyloid-specific dyes and dose-dependent cytotoxicity by a late apoptosis mechanism. […] The disorder is caused by mutations in the genes that code for the enzyme complex responsible for the breakdown of BCAAs. As a result, individuals with MSUD accumulate high levels of BCAAs in blood and tissues, which can cause a range of neurological symptoms. […] Despite being first described almost 70 years ago, the precise etiological mechanisms underlying MSUD pathogenesis remain poorly understood. […] Recently, several metabolites associated with various IEMs, including both single amino acids and nucleobases, were demonstrated to self-assemble and form amyloid-like fibrillar assemblies.

• #16 Branched-Chain Amino Acid Assembly into Amyloid-like Fibrils Provides a New Paradigm for Maple Syrup Urine Disease Pathology

  https://www.mdpi.com/1422-0067/24/21/15999

  Here, we present novel evidence that supports the hypothesis that elevated levels of BCAAs trigger the self-assembly and subsequent aggregation of these amino acids, resulting in the formation of amyloid-like structures. […] Overall, our findings suggest an innovative mechanism for MSUD pathology, involving the self-assembly of BCAAs, which results in the formation of amyloid-like structures. […] Our study provides a new perspective on the pathogenesis of MSUD and highlights the potential of amyloid inhibitors as a therapeutic strategy for this devastating disease.

• #17 Maple Syrup Urine Disease In Adulthood: Challenges And Management – Klarity Health Library

  https://my.klarity.health/maple-syrup-urine-disease-in-adulthood-challenges-and-management/

  The oxidative decarboxylation of -ketoacids is initiated by the BCKAD complex during the second phase of BCAA catabolism. Increased amounts of BCAA in the body as a result of pathogenic flaws in these constituents result in MSUD, which causes immune system, skeletal muscle, and central nervous system (CNS) dysfunction, among other symptoms. […] Glutamate concentrations within the brain are stabilized by the metabolism of BCAAs. A variety of neurological illnesses in patients can be brought on by abnormalities in glutamate production, which arise from disorders associated with the metabolizing process of the branched-chain amino acids (BCAAs). […] Elevated leucine levels can interfere with other essential amino acids in the central nervous system (CNS), such as tyrosine, which plays a key role in protein signalling. This disruption can alter nitrogen balance, further reducing glutamate levels, and lead to brain swelling by disturbing water regulation in the subcortical grey matter.

• #18 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

  The treatment includes a protein-restricted diet and supplementation with a specialized formula containing essential amino acids (excluding BCAA) and micronutrients to prevent the onset of neurological symptoms. […] The principle goal of treatment in these patients is the reduction of the leucine level by 500 to 1000 moles/L/day. […] Sodium phenylbutyrate reduces BCAA and can be effective in patients with intermediate MSUD. However, its effectiveness is controversial and more studies are needed. […] The management required for this group of patients varies based on the type of MSUD. For intermediate MSUD, leucine restriction branched chain free amino acids and an ER are necessary. […] For intermittent MSUD, may only require moderate protein restriction (no branched chain free amino acids) and an ER. […] In E3-deficiency patients, a BCAA-restricted diet does not reverse or prevent ongoing symptoms, but can maintain blood BCAA concentrations within target ranges.

• #19 Dietary Management of a Patient with Both Maple Syrup Urine Disease and Type I Diabetes – The Journal of Pediatric Research

  https://jpedres.org/articles/dietary-management-of-a-patient-with-both-maple-syrup-urine-disease-and-type-i-diabetes/doi/jpr.89421

  Maple Syrup Urine disease (MSUD) is caused by the deficiency of the branched chain 2-ketoacid dehydrogenase complex. […] Maple Syrup Urine disease (MSUD) is caused by the deficiency of the branched chain 2-ketoacid dehydrogenase (BCKD) complex, the second common step in the catabolism of the three branched chain amino acids (BCAA), leucine, isoleucine and valine. […] MSUD, also known as branched-chain ketoaciduria, is a disorder affecting the BCAA. […] The activity of the BCKD complex, the rate-limiting enzyme in the BCAA catabolism, has clearly diminished. […] Demonstration of the mechanism underlying the presence of two disorders together, MSUD and TIDM could be accepted as coincidence in this patient. […] The goals of medical nutrition therapy in MSUD are to rapidly reduce toxic metabolites by restricting dietary BCAA to amounts allowing individuals to achieve and maintain plasma BCAA amino acid concentrations within the targeted treatment ranges; reduce catabolism; promote anabolism; monitor nutritional status and alter intake to promote normal growth, development and health maintenance; evaluate thiamin responsiveness if the individual has residual BCKD activity; and supplement with thiamin if the individual is responsive.

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

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

  As a result, the amino acids build up, and so do their toxic byproducts. This leads to a metabolic crisis. […] The mutations may appear on any of the three genes responsible for enzymes breaking down the three amino acids. These genes are: BCKDHA, BCKDHB, DBT. […] The toxins in your system can damage several organs and body systems. Complications include: Brain damage, neurological problems and developmental delays. […] Healthcare providers manage MSUD by controlling the level of the three amino acids (leucine, isoleucine and valine) in your body and providing emergency treatment to reverse a metabolic crisis if one arises. […] Since 2004, liver transplants have successfully treated people with classic MSUD. A new liver can produce the enzymes needed to break down the three amino acids. After a liver transplant, you can eat an unrestricted diet, live without symptoms, and avoid further symptoms or complications.

Zobacz więcej