RESUMO
BACKGROUND AND OBJECTIVES: The literature about oral manifestations and dental management in maple syrup urine disease (MSUD) is sparse. The aim of this report is to present a new case of MSUD with special emphasis on oral findings and to review the relevant literature. METHOD: A case report of a 4-year-old boy with MSUD was described according to the CARE guidelines for describing case reports. Scoping review of relevant literature was performed, according to the PRISMA-ScR guidelines, by searching PubMed, Medline, Embase, and the grey literature for articles describing dental management and/or oral manifestations in MSUD. RESULTS: The initial search identified 219 articles, but only 4 met the inclusion criteria. Rampant caries and plaque induced gingivitis were the main oro-dental findings in MSUD. Other oral findings included enamel hypoplasia, skeletal abnormalities, and abnormal oral behaviors. Disease-related factors appeared to play a major role in the development of the observed oral phenotype. CONCLUSION: Oral health in MSUD seems to be influenced by the reliance on semi-synthetic diet and associated neurocognitive complications. Tailored oral health promotional interventions should be included in the multidisciplinary management of patients with MSUD.
Assuntos
Doença da Urina de Xarope de Bordo , Fenótipo , Humanos , Masculino , Pré-Escolar , Doença da Urina de Xarope de Bordo/complicações , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/terapia , Cárie Dentária/terapia , Cárie Dentária/complicações , Gengivite/terapia , Gengivite/etiologiaRESUMO
BACKGROUND: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). OBJECTIVE: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. RESULTS: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients' quality of life (QOL) was not significantly improved. CONCLUSIONS: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.
Assuntos
Acidose Láctica/dietoterapia , Acidose Láctica/mortalidade , Dieta Cetogênica/mortalidade , Nutrição Enteral/mortalidade , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/mortalidade , Acidose Láctica/genética , Adolescente , Criança , Pré-Escolar , Dieta Cetogênica/métodos , Nutrição Enteral/métodos , Feminino , Gastrostomia , Humanos , Lactente , Masculino , Doença da Urina de Xarope de Bordo/genética , Mutação , Qualidade de VidaRESUMO
Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore appropriate concentration relationships among circulating amino acids, and does not fully prevent cognitive and psychiatric disabilities. Liver transplantation eliminates the need for a prescription diet and safeguards patients from life-threatening metabolic crises, but is associated with predictable morbidities and does not reverse pre-existing neurological sequelae. There is a critical unmet need for safe and effective disease-modifying therapies for MSUD which can be implemented early in life. The biochemistry and physiology of MSUD and its response to liver transplantation afford key insights into the design of new therapies based on gene replacement or editing.
Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Aminoácidos de Cadeia Ramificada/metabolismo , Biomarcadores/sangue , Leucina/sangue , Transplante de Fígado , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/terapia , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Dieta , Feminino , Homozigoto , Humanos , Lactente , Leucina/metabolismo , Masculino , Doença da Urina de Xarope de Bordo/genética , Doença da Urina de Xarope de Bordo/metabolismo , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , FenótipoRESUMO
We present a one-year-old girl with maple syrup urine disease with dermatitis secondary to the restriction of amino acids as part of the treatment. We present the clinical evolution and histopathological correlation.
Assuntos
Aminoácidos de Cadeia Ramificada/administração & dosagem , Dermatite/etiologia , Leucina/deficiência , Desnutrição/complicações , Doença da Urina de Xarope de Bordo/complicações , Pele/patologia , Aminoácidos de Cadeia Ramificada/sangue , Dermatite/patologia , Feminino , Humanos , Lactente , Doença da Urina de Xarope de Bordo/dietoterapiaRESUMO
Maple syrup urine disease (MSUD) is an inherited deficiency of the branched-chain α-keto dehydrogenase complex, characterized by accumulation of the branched-chain amino acids (BCAAs) and their respective branched chain α-keto-acids (BCKAs), as well as by the presence of alloisoleucine (Allo). Studies have shown that oxidative stress is involved in the pathophysiology of MSUD. In this work, we investigated using the comet assay whether Allo, BCAAs and BCKAs could induce in vitro DNA damage, as well as the influence of l-Carnitine (L-Car) upon DNA damage. We also evaluated urinary 8-hydroxydeoguanosine (8-OHdG) levels, an oxidative DNA damage biomarker, in MSUD patients submitted to a restricted diet supplemented or not with L-Car. All tested concentrations of metabolites (separated or incubated together) induced in vitro DNA damage, and the co-treatment with L-Car reduced these effects. We found that Allo induced the higher DNA damage class and verified a potentiation of DNA damage induced by synergistic action between metabolites. In vivo, it was observed a significant increase in 8-OHdG levels, which was reversed by L-Car. We demonstrated for the first time that oxidative DNA damage is induced not only by BCAAs and BCKAs but also by Allo and we reinforce the protective effect of L-Car.
Assuntos
Aminoácidos/administração & dosagem , Carnitina/uso terapêutico , Dano ao DNA , Suplementos Nutricionais , Doença da Urina de Xarope de Bordo , Substâncias Protetoras/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Aminoácidos/sangue , Aminoácidos/urina , Criança , Pré-Escolar , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Humanos , Doença da Urina de Xarope de Bordo/sangue , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/genética , Doença da Urina de Xarope de Bordo/urinaRESUMO
PURPOSE: Maple Syrup Urine Disease (MSUD) is a rare disorder of branched-chain amino acid catabolism associated with encephalopathy from accumulation of leucine. Leucine is closely monitored during normal growth and particularly during acute illness. As most hospitals do not have access to rapid plasma amino acid quantification, the initial management is often empirical. A model describing the reduction of plasma leucine in hyperleucinemic patients on leucine-free formula would help to guide management and optimize testing frequency. METHODS: We retrospectively reviewed charts from 15 MSUD patients comprising 29 episodes of hyperleucinemia that were managed with leucine-free formula. Episodes were categorized by clinical presentation. RESULTS: Upon leucine restriction, plasma leucine concentrations fell exponentially at a rate proportional to approximately 50% of the starting value over each 24-hour period. Recovery appears to be sensitive to clinical status and triggering event of the hyperleucinemic episode. Patients with upper respiratory infections generally recovered slowly, while cases of dietary non-adherence resolved more quickly. CONCLUSION: This general model may help anticipate leucine levels during clinical management of MSUD patients when using nutritional support and leucine-free formula. The response of individual patients may vary depending on clinical status and triggering factors.
Assuntos
Dieta , Leucina/sangue , Leucina/metabolismo , Doença da Urina de Xarope de Bordo/dietoterapia , Acidose/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doença da Urina de Xarope de Bordo/sangue , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Maple syrup urine disease (MSUD) is a metabolic disorder that is caused by deficiency of branched-chain α-keto acid dehydrogenase complex. Although accumulation of toxic metabolites is associated with neurotoxicity, mechanisms underlying brain damage remain unclear. Aim of this study is to evaluate thiol/disulphide homeostasis as a novel indicator of oxidative stress in MSUD patients under treatment. Twenty patients with MSUD and 20 healthy individuals were included in study. All patients were under regular follow-up and had a good metabolic control. Serum native thiol (-SH), total thiol (-SH + -S-S-), disulphide (-S-S) levels were measured in all subjects. Disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated from these values. Simultaneous blood sampling for plasma quantitative amino acid analysis was performed in both groups. Any significant difference was not observed in -SH, -SH + -S-S-, -S-S levels between two groups. In addition no increase of disulphide/native thiol and disulphide/total thiol ratios was detected in patient group. This study is the first study that evaluates dynamic thiol/disulphide homeostasis as an indicator of oxidative stress in MSUD patients. Among previous studies that were made to determine oxidative stress in treated MSUD patients, this study had the largest sample size also. In recent studies, it was claimed that oxidative stress could be responsible from neurotoxicity even in treated patients. Here, dynamic thiol/disulfide homeostasis status showed that providing good metabolic control in MSUD patients prevent oxidative stress. Under regular follow-up and good compliance with diet, additional antioxidant therapies would possibly not be necessary.
Assuntos
Dissulfetos/sangue , Homeostase/fisiologia , Doença da Urina de Xarope de Bordo/metabolismo , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/sangue , Adolescente , Criança , Pré-Escolar , Dieta com Restrição de Proteínas , Feminino , Humanos , Lactente , Masculino , Doença da Urina de Xarope de Bordo/dietoterapiaRESUMO
BACKGROUND: Special diet with restricted branched-chain-amino-acids used for treating maple syrup urine disease can lead to specific amino acid deficiencies. CASE CHARACTERISTICS: We report a neonate who developed skin lesions due to isoleucine deficiency while using specialised formula. INTERVENTION/OUTCOME: Feeds were supplemented with expressed breast milk. This caused biochemical and clinical improvement with resolution of skin lesions. MESSAGE: Breast milk is a valuable and necessary adjunct to specialized formula in maple syrup urine disease to prevent specific amino acid deficiency in the neonatal period.
Assuntos
Isoleucina , Doença da Urina de Xarope de Bordo , Acrodermatite , Aleitamento Materno , Diagnóstico Diferencial , Humanos , Fórmulas Infantis , Recém-Nascido , Isoleucina/administração & dosagem , Isoleucina/deficiência , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/genética , Doença da Urina de Xarope de Bordo/fisiopatologia , Zinco/deficiênciaRESUMO
RATIONALE, AIMS AND OBJECTIVES: Evidence and consensus-based guidelines for nutrition management of maple syrup urine disease (MSUD) were developed as part of a project to create nutrition guidelines for inherited metabolic disorders identified through newborn screening. The objective of this study was to describe and evaluate the role of evidence analysts in the systematic review phase of guideline development to improve quality of process and output and inform future guideline development projects. METHODS: Recruitment, training and output of evidence analysts were documented throughout the MSUD project. The role of analysts was to critically review and rate the scientific quality of published literature and abstract pertinent information using quality checklists and abstraction worksheets. A secure, web-based application was developed to standardize the process and establish permanent documentation. Analysts completed a post-project survey on perceptions of their role, training and the evidence analysis process. RESULTS: Of 23 recruits, 65% (15) completed evidence analyst training; 73% of those (11) participated in the analysis of 98 literature articles. Analysts reviewed a median of four articles (range 1-16) with median productivity of 1.1 articles per month. All analysts surveyed (n = 9) understood their role and agreed that training was adequate; 100% agreed that analyst involvement was critical in developing guidelines for MSUD. CONCLUSION: Evidence analysts played a key role in appraising and abstracting evidence to develop nutrition guidelines for MSUD. With critical improvements to the process, particularly more stringent and systematic evaluation and documentation of analyst performance related to productivity and quality, we will continue to recruit, train and support evidence analysts in evidence-based guideline development projects.
Assuntos
Medicina Baseada em Evidências/organização & administração , Doença da Urina de Xarope de Bordo/dietoterapia , Guias de Prática Clínica como Assunto/normas , Medicina Baseada em Evidências/normas , Humanos , Erros Inatos do Metabolismo/dietoterapia , Nutricionistas , Melhoria de QualidadeRESUMO
Maple syrup urine disease (MSUD) is a disorder of branched-chain amino acids (BCAA). The defect in the branched-chain α-keto acid dehydrogenase complex activity leads to an accumulation of these compounds and their corresponding α-keto-acids and α-hydroxy-acids. Studies have shown that oxidative stress may be involved in neuropathology of MSUD. L-carnitine (L-car), which has demonstrated an important role as antioxidant by reducing and scavenging free radicals formation and by enhancing the activity of antioxidant enzymes, have been used in the treatment of some metabolic rare disorders. This study evaluated the oxidative stress parameters, di-tyrosine, isoprostanes and antioxidant capacity, in urine of MSUD patients under protein-restricted diet supplemented or not with L-car capsules at a dose of 50 mg kg(-1) day(-1). It was also determined urinary α-keto isocaproic acid levels as well as blood free L-car concentrations in blood. It was found a deficiency of carnitine in patients before the L-car supplementation. Significant increases of di-tyrosine and isoprostanes, as well as reduced antioxidant capacity, were observed before the treatment with L-car. The L-car supplementation induced beneficial effects on these parameters reducing the di-tyrosine and isoprostanes levels and increasing the antioxidant capacity. It was also showed a significant increase in urinary of α-ketoisocaproic acid after 2 months of L-car treatment, compared to control group. In conclusion, our results suggest that L-car may have beneficial effects in the treatment of MSUD by preventing oxidative damage to the cells and that urine can be used to monitorize oxidative damage in patients affected by this disease.
Assuntos
Biomarcadores/urina , Suplementos Nutricionais , Doença da Urina de Xarope de Bordo/urina , Aminoácidos/urina , Análise de Variância , Antioxidantes/metabolismo , Criança , Pré-Escolar , Dinoprosta/análogos & derivados , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Isoprostanos/urina , Cetoácidos/urina , Masculino , Doença da Urina de Xarope de Bordo/dietoterapia , Espectrometria de Massas em Tandem , Tirosina/urinaRESUMO
BACKGROUND: Conventional therapy for patients with maple syrup urine disease (MSUD) entails restriction of protein intake to maintain acceptable levels of the branched chain amino acid, leucine (LEU), monitored in blood. However, no data exists on the correlation between brain and blood LEU with protein restriction, and whether correction in blood is reflected in brain. METHODS: To address this question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for quantitative amino acid analyses. RESULTS: LEU and valine (VAL) levels in all brain regions improved on average 28% when shifting from 19% to 6% protein, whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in brain regions did not improve, while the SE level improved 24% with low-protein consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) were 362-434 µM, consistent with human values considered within control. Nonetheless, numerous amino acids in brain regions remained abnormal despite protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine (SER). To assess the specificity of these anomalies, we piloted preliminary studies in hyperphenylalaninemic mice, modeling another large neutral aminoacidopathy. Employing an identical dietary regimen, we found remarkably consistent abnormalities in GLN, ASP, and GLU. CONCLUSIONS: Our results suggest that blood amino acid analysis may be a poor surrogate for assessing the outcomes of protein restriction in the large neutral amino acidopathies, and further indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may contribute to long-term neurocognitive dysfunction in these disorders.
Assuntos
Aminoácidos/metabolismo , Encéfalo/metabolismo , Proteínas Alimentares/administração & dosagem , Modelos Animais de Doenças , Doença da Urina de Xarope de Bordo/dietoterapia , Aminoácidos/sangue , Animais , Doença da Urina de Xarope de Bordo/metabolismo , Doença da Urina de Xarope de Bordo/fisiopatologia , Camundongos , Reação em Cadeia da PolimeraseRESUMO
In an effort to increase harmonization of care and enable outcome studies, the Genetic Metabolic Dietitians International (GMDI) and the Southeast Regional Newborn Screening and Genetics Collaborative (SERC) are partnering to develop nutrition management guidelines for inherited metabolic disorders (IMD) using a model combining both evidence- and consensus-based methodology. The first guideline to be completed is for maple syrup urine disease (MSUD). This report describes the methodology used in its development: formulation of five research questions; review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; and expert input through Delphi surveys and a nominal group process. This report includes the summary statements for each research question and the nutrition management recommendations they generated. Each recommendation is followed by a standardized rating based on the strength of the evidence and consensus used. The application of technology to build the infrastructure for this project allowed transparency during development of this guideline and will be a foundation for future guidelines. Online open access of the full, published guideline allows utilization by health care providers, researchers, and collaborators who advise, advocate and care for individuals with MSUD and their families. There will be future updates as warranted by developments in research and clinical practice.
Assuntos
Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/cirurgia , Fatores Etários , Dieta , Suplementos Nutricionais , Gerenciamento Clínico , Medicina Baseada em Evidências , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Transplante de Fígado , Masculino , Doença da Urina de Xarope de Bordo/sangue , Guias de Prática Clínica como Assunto , GravidezRESUMO
INTRODUCTION: The development in therapeutic strategies has increased survival of children affected by inborn errors of metabolism with restricted diet (IEMRD). These diseases have mild- and long-term consequences on the health. Little is known about the impact on the quality of life (QoL) of children and their families. The aims of this study were: to compare the QoL of the children and parents affected by IEMRD with the QoL of the general population and one pathology associated with long-term consequences. PATIENTS AND METHODS: This cross-sectional study was performed at the French Reference Center for inborn metabolic disorders (Marseille, France). Inclusion criteria were: a child with a diagnosis of organic aciduria, urea cycle defect, or maple syrups urine disease (MSUD). Socio-demographics, clinical data, and QoL were recorded. RESULTS: Twenty-one of 32 eligible families were included during a planned routine visit. Ten (47%, 95% CI 27-69%) children were affected by organic aciduria, six (29%, 95% CI 10-48%) by urea cycle defects, and five (24%, 95% CI 6-42%) by MSUD. Among the younger children, the general well-being was significantly lower in the children with IEMRD than in the leukemia children (58 ± 16 versus 76 ± 15, p = 0.012), and among the older children, the leisure activities were significantly lower in the children with IEMRD than in the leukemia children (29 ± 18 versus 62 ± 22, p < 10-3), while the relationships with teachers were better (76 ± 23 versus 60 ± 23, p = 0.01). The physical QoL score was lower in the parents than in the French norms (66 ± 21 versus 75 ± 1, p = 0.05). Factors modulating QoL were: eating and neurologic disorders, enteral nutrition, and feeding modalities. CONCLUSION: The children and the parents of children affected presented altered 'physical' and 'social' QoL scores compared with the norms and patients with leukemia and their families. Future studies based on larger cohort studies should determine the different weights of potential predictive factors of QoL.
Assuntos
Erros Inatos do Metabolismo/dietoterapia , Erros Inatos do Metabolismo/psicologia , Pais/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Intervalos de Confiança , Estudos Transversais , Feminino , França , Humanos , Masculino , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/psicologia , Prontuários Médicos , Inquéritos e Questionários , Distúrbios Congênitos do Ciclo da Ureia/dietoterapia , Distúrbios Congênitos do Ciclo da Ureia/psicologiaRESUMO
OBJECTIVE: To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. METHODS: Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. RESULTS: In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. CONCLUSION: Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.
Assuntos
Encéfalo/patologia , Doença da Urina de Xarope de Bordo/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Doença da Urina de Xarope de Bordo/dietoterapia , Neuroimagem/métodos , Adulto JovemRESUMO
Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Routine screening of newborn with tandem mass spectroscopy on the third day of life may detect elevated branched-chain amino acids in blood before the appearance of encephalopathic symptoms in MSUD cases. If undiagnosed by such a routine screening test, patients often present with encephalopathy and seizures. Clinical neurologic examination is supplemented by electroencephalography and imaging. Here, we report abnormal amplitude-integrated electroencephalography, electroencephalography, magnetic resonance imaging, and magnetic resonance imaging spectroscopy findings in a neurologically asymptomatic male newborn who was diagnosed with MSUD at the third week of life. These neurologic disturbances disappeared at the fourth month of life with appropriate special diet. Therefore, even in already asymptomatic cases, early neurologic deterioration of brain metabolism and structure can be detected with these early laboratory findings, indicating the importance of early diagnosis and management. Patients may also benefit from these investigations during the follow-up period.
Assuntos
Encefalopatias/etiologia , Deficiências do Desenvolvimento/etiologia , Doença da Urina de Xarope de Bordo/complicações , Doença da Urina de Xarope de Bordo/diagnóstico , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encefalopatias/dietoterapia , Ondas Encefálicas/fisiologia , Consanguinidade , Deficiências do Desenvolvimento/patologia , Dieta , Dieta com Restrição de Carboidratos/métodos , Eletroencefalografia , Humanos , Recém-Nascido , Inositol/metabolismo , Ácido Láctico/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Doença da Urina de Xarope de Bordo/dietoterapiaRESUMO
BACKGROUND: Acute decompensation of maple syrup urine disease (MSUD) is usually treated by enteral feeding with an amino-acid mixture without leucine (Leu), valine or isoleucine. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. We developed a new parenteral amino-acid mixture for patients with MSUD. METHODS: Seventeen decompensation episodes in four adult patients with MSUD treated with a parenteral amino-acid mixture (group P) were compared to 18 previous episodes in the same patients treated by enteral feeding (group E). RESULTS: The mean Leu concentration at presentation was similar in the groups P and E (1196.9 µmol/L and 1212.2 µmol/L, respectively). The mean decrease in the Leu concentration during the first 3 days of hospitalisation was significantly higher in group P than group E (p = 0.0026); there were no side effects. The mean duration of hospitalisation was similar (4 vs. 4.5 days, p = NS). No patient in group P deteriorated whereas one patient in group E required dialysis. CONCLUSION: This new parenteral amino-acid mixture is safe and allows efficient Leu concentration decrease during acute MSUD decompensation episodes in adults. Its use avoids the need for nasogastric tube insertion.
Assuntos
Aminoácidos/administração & dosagem , Insuficiência Cardíaca/dietoterapia , Doença da Urina de Xarope de Bordo/dietoterapia , Nutrição Parenteral , Adulto , Feminino , Alimentos Formulados , Insuficiência Cardíaca/etiologia , Hospitalização , Humanos , Masculino , Doença da Urina de Xarope de Bordo/complicações , Aceitação pelo Paciente de Cuidados de Saúde , Adulto JovemRESUMO
Objetivo: relatar caso de doença da urina do xarope de bordo (leucinose) e demonstrar como obterem-se bons resultados com o tratamento metabólico da doença. Descrição do caso: recém-nascida, desenvolveu no quinto dia de vida dificuldade de sucção, prostração e alternação de hipotonia e hipertonia axial. Foi admitida com 12 dias de vida em unidade de tratamento intensivo com crises de hipertonia, opistótono, movimentos de pedalar e apneia. Foi submetida à CPAP nasal e instituído tratamento de suporte, com triagem infecciosa negativa. A cromatografia sanguínea de aminoácidos revelou aumento pronunciado de leucina (5.986,4 nmol/mL), isoleucina (488,1 nmol/mL) e valina (755,9 mmol/mL), sendo diagnosticada leucinose e iniciado o seu tratamento metabólico. Evoluiu com melhora neurológica, ganho de peso e redução dos níveis de leucina. Recebeu alta em boas condições. Comentários: houve queda mais lenta nos níveis de leucina do que o relatado na literatura, o que pode ser explicado pelo tempo necessário para conseguir-se a dieta especial (MSUD 1) e pelo fato da mistura de aminoácidos usada na nutrição parenteral conter leucina. Poder-se-ia alcançar controle bioquímico mais rápido se houvesse disponibilidade diária da análise sérica quantitativa de aminoácidos e mais agilidade na liberação dos resultados.
Objective: Case report of the maple syrup urine disease (leucinosis) and show how to get good results with the disease metabolic treatment. Case description: newborn developed in the 5th day of life difficulty poor sucking, prostration and alternating axial hypotonia and hypertonia, was admitted with 12 days of life in the intensive treatment unit, with attacks of hypertonia, opisthotonus, paddling movements and apnea. She underwent nasal CPAP and supportive care instituted, with negative infectious screening. The blood amino acid chromatography showed a pronounced increase of leucine(5.986,4 nmol/mL), isoleucine (488,1 nmol/mL) and valine (755,9 mmol/mL), with leucinosis diagnosis and started the metabolic treatment. Evolved with neurological improvement, weight gain and decreased the levels of leucine. She was discharged in good condition. Comments: there was a slower fall in levels of leucine than that reported in the literature, which can be explained by the time needed to get the specialdiet (MSUD 1) and because the mixture of amino acids used in the parenteral nutrition contain leucine. The biochemical control could be achieved faster if there was daily availability of the quantitative analysis of serum amino acids and more speed in the release of results.
Assuntos
Humanos , Feminino , Recém-Nascido , Doença da Urina de Xarope de Bordo/dietoterapia , LeucinaRESUMO
Individuals with maple syrup urine disease (MSUD) have impaired metabolism of branched-chain amino acids (BCAA) valine, isoleucine, and leucine. Life-long dietary therapy is recommended to restrict BCAA intake and thus prevent poor neurological outcomes and death. To maintain adequate nutritional status, the majority of protein and nutrients are derived from synthetic BCAA-free medical foods with variable fatty acid content. Given the restrictive diet and the importance of omega-3 fatty acids, particularly docosahexaenoic acid (DHA), in neurological development, this study evaluated the dietary and fatty acid status of females of reproductive age with MSUD attending a metabolic camp. Healthy controls of similar age and sex were selected from existing normal laboratory data. Total lipid fatty acid concentration in plasma and erythrocytes was analyzed using gas chromatography-mass spectroscopy. Participants with MSUD had normal to increased concentrations of plasma and erythrocyte alpha linolenic acid (ALA) but significantly lower concentrations of plasma and erythrocyte docosahexaenoic acid (DHA) as percent of total lipid fatty acids compared with controls (plasma DHA: MSUD 1.03 +/- 0.35, controls 2.87 +/- 1.08; P = 0.001; erythrocyte DHA: MSUD 2.58 +/- 0.58, controls 3.66 +/- 0.80; P = 0.011). Dietary records reflected negligible or no DHA intake over the 3-day period prior to the blood draw (range 0-2 mg). These results suggest females of reproductive age with MSUD have lower blood DHA concentrations than age-matched controls. In addition, the presence of ALA in medical foods and the background diet may not counter the lack of preformed DHA in the diet. The implications of these results warrant further investigation.
Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Desnutrição/prevenção & controle , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/metabolismo , Estado Nutricional/fisiologia , Adolescente , Adulto , Fatores Etários , Criança , Eritrócitos/metabolismo , Ácidos Graxos/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Adulto Jovem , Ácido alfa-Linolênico/sangueRESUMO
Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase (BCKDH) complex. This disease is currently treated primarily by dietary restriction of branched-chain amino acids (BCAAs). However, dietary compliance is often challenging. Conversely, liver transplantation significantly improves outcomes, but donor organs are scarce and there are high costs and potential risks associated with this invasive procedure. Therefore, improved treatment options for MSUD are needed. Development of novel treatments could be facilitated by animal models that accurately mimic the human disease. Animal models provide a useful system in which to explore disease mechanisms and new preclinical therapies. Here we review MSUD and currently available animal models and their corresponding relevance to the human disorder. Using animal models to gain a more complete understanding of the pathophysiology behind the human disease may lead to new or improved therapies to treat or potentially cure the disorder.