Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.395
Filtrar
1.
PLoS One ; 15(5): e0231891, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32433684

RESUMO

OBJECTIVE: The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population. METHODS: A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI symptoms, and genotyping for 37 SI hypomorphic variants were collected. Race/ethnicity-matched SI data from the Exome Aggregation Consortium (ExAC) database was used as the general population reference. RESULTS: Compared with the general population, the cumulative prevalence of hypomorphic SI variants was significantly higher in the study population (4.5% vs. 1.3%, P < .01; OR = 3.5 [95% CI: 6.1, 2.0]). Within the study population, children with a hypomorphic SI variant had a more severe GI symptom burden than those without, including: more frequent episodes of loose stools (P < .01), higher overall stool frequency (P < .01), looser stool form (P = .01) and increased flatulence (P = .02). CONCLUSION: Non-Hispanic white children with chronic idiopathic loose stools have a higher prevalence of CSID-associated hypomorphic SI variants than the general population. The GI symptom burden was greater among the study subjects with a hypomorphic SI variant than those without hypomorphic SI variants.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/patologia , Complexo Sacarase-Isomaltase/deficiência , Complexo Sacarase-Isomaltase/genética , Adolescente , Erros Inatos do Metabolismo dos Carboidratos/epidemiologia , Erros Inatos do Metabolismo dos Carboidratos/genética , Criança , Bases de Dados Factuais , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Prevalência , Estudos Prospectivos
2.
Medicine (Baltimore) ; 99(14): e19685, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243407

RESUMO

The effect of intensive insulin therapy on hyperglucagonemia in newly diagnosed type 2 diabetes (T2DM), and its associations with ß-cell function, has not been elucidated. This study assessed the effect of 12 weeks of intensive insulin therapy on hyperglucagonemia in newly diagnosed T2DM and its associations with ß-cell function, with reference to the effects of 12 weeks of oral hypoglycemic agents (OHAs).One hundred eight patients with newly diagnosed T2DM were enrolled from January 2015 to December 2015. The patients were randomly divided to receive, for 12 weeks, either intensive insulin therapy or OHAs. Meal tolerance tests were conducted at baseline before treatment (0 week), at 12 weeks (end of treatment), and 12 months after the initiation of treatment. The levels of glucagon, proinsulin, C-peptide (CP), and blood glucose were measured at timepoints 0, 30, and 120 minutes during the meal tolerance test.Intensive insulin treatment was associated with a decrease in glucagon levels (at 0, 30, and 120 minutes) and proinsulin/CP, and an increase in the insulin-secretion index ΔCP30/ΔG30 and ΔCP120/ΔG120, at 12 weeks and 12 months during the follow-up, compared with the corresponding effects of OHAs. Intensive insulin therapy could reduce but failed to normalize glucagon levels at 12 weeks. There were no correlations between the change of percentages in total area under the curve of glucagon and other glycemic parameters (proinsulin/CP; ΔCP30/ΔG30; or ΔCP120/ΔG120). Patients who received intensive insulin therapy were more likely to achieve their target glycemic goal and remission, compared with those who received OHAs.Short-term intensive insulin therapy facilitates the improvement of both ß-cell and α-cell function in newly diagnosed T2DM mellitus. Decline of ß-cell secretion and concomitant α-cell dysfunction may both be involved in the pathogenesis of T2DM.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Secretoras de Glucagon/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Esquema de Medicação , Feminino , Glucagon/sangue , Glucagon/efeitos dos fármacos , Teste de Tolerância a Glucose , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
4.
Yonsei Med J ; 60(12): 1209-1215, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769253

RESUMO

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic-clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.


Assuntos
Variação Biológica da População , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/patologia , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Adulto , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Fenótipo , Qualidade de Vida , Estudos Retrospectivos
5.
Biomed Res Int ; 2019: 3261279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781611

RESUMO

Aim: To determine whether the area of the foveal avascular zone (FAZ), as a morphological indicator of the microcirculation of the perifoveal capillary network, changes in the carbohydrate metabolism disorders during pregnancy (the gestational age of patients with gestational diabetes mellitus (GDM) and preexisting diabetes (PexD)). Methods: Ten normal individuals and 41 eyes of 41 patients, 28 with GDM and 13 with PexD, were studied. A 3 × 3 mm area of the FAZ of the superficial capillary plexus layer (SCP) and the deep capillary plexus layer (DCP) was determined by optical coherence tomography angiography (OCTA; RS-3000 Advance, NIDEK). The significance of the correlation between the size of the FAZ and the weeks of pregnancy was determined. Results: The area of the FAZ of the SCP was 0.38 ± 0.11 mm2 (normal eyes), 0.41 ± 0.16 mm2 (GDM), and 0.43 ± 0.10 mm2 (PexD). The area of the FAZ of the DCP was 0.78 ± 0.23 mm2 (normal eyes), 0.69 ± 0.16 mm2 (GDM), and 0.79 ± 0.25 mm2 (PexD). No significant difference in the FAZ sizes was observed between the groups. The average number of weeks of pregnancy was 24.1 ± 8.2 weeks in the eyes with GDM and 23.3 ± 11.4 weeks in the eyes with PexD (P > 0.05). Significant correlations were found between the size of the FAZ of the SCP and the number of weeks (r = 0.37, P=0.04 for GDM, and r = 0.49, P=0.04 for PexD, Spearman's rank-order correlation coefficient). Conclusions: For GDM and PexD under established glycemic control, the area of the FAZ is not affected, but vascular changes occurred at the early phase of pregnancy.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Fóvea Central/metabolismo , Macula Lutea/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Carboidratos/patologia , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Diabetes Gestacional/diagnóstico por imagem , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Feminino , Fóvea Central/irrigação sanguínea , Fóvea Central/diagnóstico por imagem , Fóvea Central/patologia , Humanos , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Masculino , Gravidez , Complicações na Gravidez/patologia , Tomografia de Coerência Óptica
6.
Nutrients ; 11(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581549

RESUMO

Diseases involving inflammation and oxidative stress can be exacerbated by high blood glucose levels. Due to tight metabolic regulation, safely reducing blood glucose can prove difficult. The ketogenic diet (KD) reduces absolute glucose and insulin, while increasing fatty acid oxidation, ketogenesis, and circulating levels of ß-hydroxybutyrate (ßHB), acetoacetate (AcAc), and acetone. Compliance to KD can be difficult, so alternative therapies that help reduce glucose levels are needed. Exogenous ketones provide an alternative method to elevate blood ketone levels without strict dietary requirements. In this study, we tested the changes in blood glucose and ketone (ßHB) levels in response to acute, sub-chronic, and chronic administration of various ketogenic compounds in either a post-exercise or rested state. WAG/Rij (WR) rats, a rodent model of human absence epilepsy, GLUT1 deficiency syndrome mice (GLUT1D), and wild type Sprague Dawley rats (SPD) were assessed. Non-pathological animals were also assessed across different age ranges. Experimental groups included KD, standard diet (SD) supplemented with water (Control, C) or with exogenous ketones: 1, 3-butanediol (BD), ßHB mineral salt (KS), KS with medium chain triglyceride/MCT (KSMCT), BD acetoacetate diester (KE), KE with MCT (KEMCT), and KE with KS (KEKS). In rested WR rats, the KE, KS, KSMCT groups had lower blood glucose level after 1 h of treatment, and in KE and KSMCT groups after 24 h. After exercise, the KE, KSMCT, KEKS, and KEMCT groups had lowered glucose levels after 1 h, and in the KEKS and KEMCT groups after 7 days, compared to control. In GLUT1D mice without exercise, only KE resulted in significantly lower glucose levels at week 2 and week 6 during a 10 weeks long chronic feeding study. In 4-month and 1-year-old SPD rats in the post-exercise trials, blood glucose was significantly lower in KD and KE, and in KEMCT groups, respectively. After seven days, the KSMCT group had the most significantly reduced blood glucose levels, compared to control. These results indicate that exogenous ketones were efficacious in reducing blood glucose levels within and outside the context of exercise in various rodent models of different ages, with and without pathology.


Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Acetoacetatos/farmacologia , Glicemia/efeitos dos fármacos , Butileno Glicóis/farmacologia , Erros Inatos do Metabolismo dos Carboidratos/terapia , Dieta Cetogênica , Suplementos Nutricionais , Epilepsia Tipo Ausência/terapia , Proteínas de Transporte de Monossacarídeos/deficiência , Animais , Biomarcadores , Glicemia/metabolismo , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Modelos Animais de Doenças , Regulação para Baixo , Epilepsia Tipo Ausência/sangue , Epilepsia Tipo Ausência/genética , Epilepsia Tipo Ausência/fisiopatologia , Transportador de Glucose Tipo 1/deficiência , Transportador de Glucose Tipo 1/genética , Masculino , Camundongos Knockout , Proteínas de Transporte de Monossacarídeos/sangue , Proteínas de Transporte de Monossacarídeos/genética , Esforço Físico , Ratos Sprague-Dawley , Descanso , Fatores de Tempo
7.
Nutrients ; 11(10)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557950

RESUMO

Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder of carbohydrate maldigestion and malabsorption caused by mutations in the sucrase-isomaltase (SI) gene. SI, together with maltase-glucoamylase (MGAM), belongs to the enzyme family of disaccharidases required for breakdown of -glycosidic linkages in the small intestine. The effects of homozygote and compound heterozygote inheritance trait of SI mutations in CSID patients have been well described in former studies. Here we propose the inclusion of heterozygote mutation carriers as a new entity in CSID, possibly presenting with milder symptoms. The hypothesis is supported by recent observations of heterozygote mutation carriers among patients suffering from CSID or patients diagnosed with functional gastrointestinal disorders. Recent studies implicate significant phenotypic heterogeneity depending on the character of the mutation and call for more research regarding the correlation of genetics, function at the cellular and molecular level and clinical presentation. The increased importance of SI gene variants in irritable bowel syndrome (IBS) or other functional gastrointestinal disorders FGIDs and their available symptom relief diets like fermentable oligo-, di-, mono-saccharides and polyols FODMAPs suggest that the heterozygote mutants may affect the disease development and treatment.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/genética , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Síndromes de Malabsorção/genética , Complexo Sacarase-Isomaltase/deficiência , Humanos , Síndrome do Intestino Irritável/genética , Mutação , Complexo Sacarase-Isomaltase/genética
8.
Ann Clin Transl Neurol ; 6(9): 1923-1932, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31464092

RESUMO

Proper development and function of the mammalian brain is critically dependent on a steady supply of its chief energy source, glucose. Such supply is mediated by the glucose transporter 1 (Glut1) protein. Paucity of the protein stemming from mutations in the associated SLC2A1 gene deprives the brain of glucose and triggers the infantile-onset neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). Considering the monogenic nature of Glut1 DS, the disease is relatively straightforward to model and thus study. Accordingly, Glut1 DS serves as a convenient paradigm to investigate the more general cellular and molecular consequences of brain energy failure. Here, we review how Glut1 DS models have informed the biology of a prototypical brain energy failure syndrome, how these models are facilitating the development of promising new treatments for the human disease, and how important insights might emerge from the study of Glut1 DS to illuminate the myriad conditions involving the Glut1 protein.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/terapia , Dieta Cetogênica , Terapia Genética , Transportador de Glucose Tipo 1/genética , Proteínas de Transporte de Monossacarídeos/deficiência , Triglicerídeos/uso terapêutico , Encéfalo/metabolismo , Erros Inatos do Metabolismo dos Carboidratos/tratamento farmacológico , Erros Inatos do Metabolismo dos Carboidratos/genética , Humanos , Proteínas de Transporte de Monossacarídeos/genética , Mutação
9.
Medicine (Baltimore) ; 98(33): e16828, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415402

RESUMO

RATIONALE: Congenital glucose-galactose malabsorption (CGGM) is a rare, autosomal recessive, hereditary disease that usuallypresents in newborns. CGGM manifests as severe diarrhea, hyperosmolar dehydration, and malnutrition. It does not respond to routine treatment and often is life-threatening. PATIENT CONCERNS: We described a Chinese infant girl with refractory diarrhea, who suffered from severe dehydration and malnutrition even if with fluid replacement therapy and fed with several special formulas. DIAGNOSES: The genetic analysis identified CGGM with SLC5A1 mutations. c.1436G > C (p.R479T) was a novel mutation. INTERVENTIONS: The patient was managed by free-glucose and galactose formula, and then special low-carbohydrate dietary therapy. OUTCOMES: The patient improved immediately after starting a free-glucose and galactose formula, and kept healthy with special low-carbohydrate diet. She had been followed up with nutritional management for 20 months. LESSONS: This report highlights the importance of differential diagnosis of congenital diarrhea and enteropathies. For CGGM, free-glucose and galactose milk powder was the most effective treatment. Low-carbohydrate diet gradually introduced was still a great challenge that requires continuing guidance from child nutritionists and dietitians. Long-term nutrition management was extremely important to ensure the normal growth and development of children.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/tratamento farmacológico , Dieta com Restrição de Carboidratos/métodos , Fórmulas Infantis , Síndromes de Malabsorção/tratamento farmacológico , Erros Inatos do Metabolismo dos Carboidratos/genética , China , Feminino , Galactose , Glucose , Humanos , Recém-Nascido , Síndromes de Malabsorção/genética , Mutação , Transportador 1 de Glucose-Sódio/genética
11.
Nutrients ; 11(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349661

RESUMO

The classical ketogenic diet (cKD) is an isocaloric, high fat, very low-carbohydrate diet that induces ketosis, strongly influencing leptin and ghrelin regulation. However, not enough is known about the impact of a long-term cKD. This study evaluated the effects of a 12-month cKD on ghrelin and leptin concentrations in children, adolescents and adults affected by the GLUT1-Deficiency Syndrome or drug resistant epilepsy (DRE). We also investigated the relationship between the nutritional status, body composition and ghrelin and leptin variations. We carried out a longitudinal study on 30 patients: Twenty-five children and adolescents (15 females, 8 ± 4 years), and five adults (two females, 34 ± 16 years). After 12-monoths cKD, there were no significant changes in ghrelin and leptin, or in the nutritional status, body fat, glucose and lipid profiles. However, a slight height z-score reduction (from -0.603 ± 1.178 to -0.953 ± 1.354, p ≤ 0.001) and a drop in fasting insulin occurred. We found no correlations between ghrelin changes and nutritional status and body composition, whereas leptin changes correlated positively with variations in the weight z-score and body fat (ρ = 0.4534, p = 0.0341; ρ = 0.5901, p = 0.0135; respectively). These results suggest that a long-term cKD does not change ghrelin and leptin concentrations independently of age and neurological condition.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Dieta Cetogênica , Epilepsia Resistente a Medicamentos/dietoterapia , Grelina/sangue , Leptina/sangue , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Adulto , Biomarcadores/sangue , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/sangue , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Feminino , Humanos , Itália , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte de Monossacarídeos/sangue , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Nutrients ; 11(7)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31330987

RESUMO

BACKGROUND: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare, genetically determined neurological disorder, for which Ketogenic Diet (KD) represents the gold standard life-long treatment. The aim of this study is to investigate health related quality of life in a well characterized cohort of patients affected by GLUT1DS treated with KD, evaluating factors that can influence patients' and parents' quality of life perception. METHODS: This is a double center exploratory research study. A postal survey with auto-administrable questionnaires was conducted among 17 subjects (aged 3-22 years) with diagnosis of GLUT1DS, receiving a stable KD treatment for more than 1 year. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales was adopted. Clinical variables analyzed in relation to quality of life were frequency of epileptic seizures and movement disorder since KD introduction, presence of intellectual disability (ID), and KD ratio. RESULTS: Quality of life global scores were impaired both in parents' and children's perspectives, with a significant concordance. Taking into consideration subscales, the average was 64.17 (range 10-100) for physical functioning, 74.23 (range 30-100) for emotional functioning, 62.64 (range 10-100) for social functioning, and 56 (range 15-92) for school functioning. CONCLUSIONS: In patients with GLUT1DS the quality of life perception is comparable to that of other patients with chronic disease. In our sample, the presence of movement disorder seems to be a crucial element in quality of life perception.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Dieta Cetogênica , Proteínas de Transporte de Monossacarídeos/deficiência , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Dieta Cetogênica/psicologia , Emoções/fisiologia , Feminino , Humanos , Masculino , Transtornos dos Movimentos/epidemiologia , Pais , Convulsões/epidemiologia , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
13.
Brain Dev ; 41(10): 854-861, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31326153

RESUMO

INTRODUCTION: The neurodevelopmental outcomes of young infants with hypoglycorrhachia that is comparable to glucose transporter 1 deficiency syndrome (GLUT1DS), i.e. cerebrospinal fluid (CSF) glucose ≤40 mg/dL and CSF lactate <2.2 mM without causes of secondary hypoglycorrhachia are unknown. This study investigated the developmental outcomes and possibility of GLUT1DS in infants with hypoglycorrhachia, or low CSF glucose concentration. MATERIAL AND METHODS: 1655 neurologically asymptomatic infants aged <4 months had CSF examinations for fever workup from 2006 to 2016. Among the infants with normal CSF cell counts and without isolated pathogens, there were hypoglycorrhachia group who had CSF glucose levels that were comparable to GLUT1DS, and age- and gender-matched non-hypoglycorrhachia group. Both groups were at a mean age of 5.9 ±â€¯2.4 years (ranged 1-10 years) at neurodevelopmental evaluation in 2017. Mutational analysis of solute-carrier-family 2, which facilitated the glucose transporter member 1 (SLC2A1) gene was performed. RESULTS: Among the 722 infants with normal CSF cell counts and without isolated pathogens, 30 (4.2%) had hypoglycorrhachia that was comparable to GLUT1DS. In the 25 infants with hypoglycorrhachia available for follow-up, 4 (16%) had abnormal outcomes, of which 3 (12%) had the history of mixed-type developmental delay before age 6 and 1 (4%) had type 1 diabetes mellitus. In the non-hypoglycorrhachia control group (n = 50), 2 patients (4%) showed abnormal outcomes, both with the history of pure speech delay. The hypoglycorrhachia group had a higher rate of the history of mixed-type of developmental delay than the control group (12% vs. 0%, P = 0.034). No SLC2A1 pathogenic variants were observed in the hypoglycorrhachia group. CONCLUSION: Hypoglycorrhachia may be a potential biomarker for neurodevelopmental delay instead of for GLUT1DS in neurologically asymptomatic young infants.


Assuntos
Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glucose/líquido cefalorraquidiano , Erros Inatos do Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Estudos de Casos e Controles , Pré-Escolar , Análise Mutacional de DNA , Feminino , Glucose/metabolismo , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Masculino , Proteínas de Transporte de Monossacarídeos/deficiência , Proteínas de Transporte de Monossacarídeos/genética , Transtornos do Neurodesenvolvimento/etiologia , Prevalência
14.
Eur J Med Genet ; 62(8): 103708, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31247379

RESUMO

Ribose 5-phosphate isomerase deficiency is a rare genetic leukoencephalopathy caused by pathogenic sequence variants in RPIA, that encodes ribose 5-phosphate isomerase, an enzyme in the pentose phosphate pathway. Till date, only three individuals with ribose 5-phosphate isomerase deficiency have been described in literature. We report on a subject with RPIA associated progressive leukoencephalopathy with elevated urine arabitol and ribitol levels and a novel missense variant c.770T > C p.(Ile257Thr) in exon 8 of RPIA. We also compare the phenotypes of all the four subjects. Our report confirms the phenotype and the genetic cause of this condition.


Assuntos
Aldose-Cetose Isomerases/deficiência , Erros Inatos do Metabolismo dos Carboidratos/genética , Leucoencefalopatias/genética , Polineuropatias/genética , Aldose-Cetose Isomerases/genética , Alelos , Erros Inatos do Metabolismo dos Carboidratos/tratamento farmacológico , Erros Inatos do Metabolismo dos Carboidratos/patologia , Humanos , Leucoencefalopatias/tratamento farmacológico , Leucoencefalopatias/patologia , Masculino , Via de Pentose Fosfato/genética , Polineuropatias/tratamento farmacológico , Polineuropatias/patologia , Ribitol/administração & dosagem , Álcoois Açúcares/administração & dosagem
15.
Brain Dev ; 41(9): 808-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31196579

RESUMO

In some patients with GLUT1 deficiency syndrome (GLUT1-DS), the diagnosis can be difficult to reach. We report a child with 2 inherited mutations suggesting an autosomal recessive transmission of SLC2A1 mutations. METHODS: The child and her parents were explored with erythrocyte 3-O-methyl-d-Glucose uptake, glucose uptake in oocytes expressing GLUT1 with the gene mutations and measure of the expression of GLUT1 at the surface of the circulating red blood cells by flow cytometry (METAglut1™ test). RESULTS: Both erythrocyte glucose uptake and glucose uptake in oocyte with the patient's mutations did not support the diagnosis of a mild GLUT1-DS phenotype with autosomal recessive transmission of SLC2A1 mutations. Instead, GLUT-1 expression at the surface of the erythrocytes appeared to better correlate with the clinical phenotypes in this family. CONCLUSION: The diagnostic value of these functional/expression tools need to be further studied with a focus on mild phenotype of GLUT1-DS.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/genética , Transportador de Glucose Tipo 1/genética , Proteínas de Transporte de Monossacarídeos/deficiência , Mutação , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Criança , Diagnóstico Diferencial , Família , Feminino , Humanos , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo
16.
J Coll Physicians Surg Pak ; 29(6): S48-S49, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142420

RESUMO

Intractable watery diarrhea presenting in the neonatal period is a relatively uncommon condition. Congenital disorders of malabsorption are among the major causes of prolonged watery diarrhea. This is the case report of a 3-month male infant born to consanguineous parents, who presented with intractable diarrhea since birth. He was failing to thrive and wasted. Persistent diarrhea lead to prolonged hospitalisation and recurrent hypernatremic dehydration. Relevant investigations clinched the diagnosis of ''congenital glucose galactose malabsorption (CGGM)''. The astute clinician should have a high index of suspicion regarding such rare causes of diarrhea in early infancy, as an appropriate rational diagnosis can lead to life-saving treatment as depicted in this case report.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Diarreia Infantil/etiologia , Carboidratos da Dieta/efeitos adversos , Síndromes de Malabsorção/dietoterapia , Síndromes de Malabsorção/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/complicações , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Erros Inatos do Metabolismo dos Carboidratos/genética , Diarreia Infantil/congênito , Dieta com Restrição de Carboidratos/métodos , Humanos , Lactente , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/congênito , Síndromes de Malabsorção/genética , Masculino , Mutação , Transportador 1 de Glucose-Sódio , Resultado do Tratamento
17.
Wiad Lek ; 72(4): 650-653, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055550

RESUMO

OBJECTIVE: Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common disease which is characterized by comorbidity. However, no comorbidity index for its assessment has been described yet. The aim of this study was to develop a new index for evaluation of comorbidity in patients with NAFLD. PATIENTS AND METHODS: Materials and methods: 226 patients with NAFLD and associated carbohydrate metabolism disorders were examined. Besides, 60 persons with subclinical hypothyroidism, 30 patients with type 2 diabetes mellitus (T2-DM) and 30 NAFLD patients were examined. 30 healthy persons formed the control group. Clinical diagnoses were based on the laboratory tests and liver sonography. A new index of comorbidity has been used. Calculation of comorbidity severity index (ComSI) includes the possible presence of NAFLD, thyroid disorders, abdominal obesity, dyslipidemia, anemia, chronic complications of T2-DM, aggravated anamnesis. RESULTS: Results: The contradiction in the calculation of the well-known comorbidity indices values (CIRS - Cumulative illness rating scale, CCI - Charlson's comorbidity index, Kaplan-Feinstein index) was shown. So, their limited suitability for using in patients with carbohydrate metabolism disorders who have NAFLD was detected. According to our results an increasing of patients' age is associated with the increasing of concomitant diseases number and with deteriorating of the patients' general condition, which is reflected in an increasing of the ComSI value. The increasing of concomitant diseases number is associated not only with the higher ComSI, but also with the number of persons with a severe comorbidity according the ComSI value. Instead, the persons without comorbidity (groups 6, 7, 8) were marked as the patients with mild or moderate disease according the ComSI. CONCLUSION: Conclusions:The new ComSI index can be used to evaluate the severity of comorbidity in patients with NAFLD.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hipotireoidismo/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Índice de Gravidade de Doença , Erros Inatos do Metabolismo dos Carboidratos/complicações , Estudos de Casos e Controles , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipotireoidismo/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico
18.
Am J Case Rep ; 20: 647-650, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31055589

RESUMO

BACKGROUND GLUT1-deficiency-syndrome (G1DS) is an autosomal dominant genetic disorder based on a mutation of the SLC2A1 gene. This mutation can lead to an encephalopathy due to abnormal glucose transport in the brain. G1DS is a rare disease, with an estimated incidence of 1: 90 000. CASE REPORT We report a case of a 10-year-old female who presented with recurrent fever, headaches, and vertigo for more than 3 days within 2 weeks following pneumonia. A bilateral mastoiditis was proven by a cerebral magnetic resonance imaging and a cranial computed tomography scan. The patient had to undergo mastoidectomy and thus, her first general anesthesia. Half a year previously she was diagnosed with G1DS. According to the standard of care, a ketogenic diet had been administered since the patient's diagnosis 6 months earlier. Our patient received a total intravenous anesthesia (TIVA) using propofol, fentanyl, and rocuronium administered without any incidents. CONCLUSIONS We recommend normoglycemia during the perioperative phase and avoidance of glucose-based medication to keep a patient's ketotic state. Our case highlights that TIVA, with the outlined medication used in this case, was safe when the patient's ketotic state and periprocedural blood glucose was monitored continuously. Nevertheless, we would suggest using remifentanil instead of fentanyl for future TIVAs due to a reduced increase in blood glucose level in our patient.


Assuntos
Anestesia Intravenosa , Anestésicos Intravenosos/administração & dosagem , Erros Inatos do Metabolismo dos Carboidratos/complicações , Proteínas de Transporte de Monossacarídeos/deficiência , Criança , Feminino , Fentanila/administração & dosagem , Humanos , Mastoidectomia , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Propofol/administração & dosagem , Rocurônio/administração & dosagem
19.
Biochim Biophys Acta Mol Basis Dis ; 1865(9): 2257-2266, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075491

RESUMO

Mutations in the gene triosephosphate isomerase (TPI) lead to a severe multisystem condition that is characterized by hemolytic anemia, a weakened immune system, and significant neurologic symptoms such as seizures, distal neuropathy, and intellectual disability. No effective therapy is available. Here we report a compound heterozygous patient with a novel TPI pathogenic variant (NM_000365.5:c.569G>A:p.(Arg189Gln)) in combination with the common (NM_000365.5:c.315G>C:p.(Glu104Asp)) allele. We characterized the novel variant by mutating the homologous Arg in Drosophila using a genomic engineering system, demonstrating that missense mutations at this position cause a strong loss of function. Compound heterozygote animals were generated and exhibit motor behavioural deficits and markedly reduced protein levels. Furthermore, examinations of the TPIArg189Gln/TPIGlu104Asp patient fibroblasts confirmed the reduction of TPI levels, suggesting that Arg189Gln may also affect the stability of the protein. The Arg189 residue participates in two salt bridges on the backside of the TPI enzyme dimer, and we reveal that a mutation at this position alters the coordination of the substrate-binding site and important catalytic residues. Collectively, these data reveal a new human pathogenic variant associated with TPI deficiency, identify the Arg189 salt bridge as critical for organizing the catalytic site of the TPI enzyme, and demonstrates that reduced TPI levels are associated with human TPI deficiency. These findings advance our understanding of the molecular pathogenesis of the disease, and suggest new therapeutic avenues for pre-clinical trials.


Assuntos
Anemia Hemolítica Congênita não Esferocítica/patologia , Erros Inatos do Metabolismo dos Carboidratos/patologia , Triose-Fosfato Isomerase/deficiência , Triose-Fosfato Isomerase/metabolismo , Alelos , Sequência de Aminoácidos , Anemia Hemolítica Congênita não Esferocítica/genética , Animais , Sequência de Bases , Erros Inatos do Metabolismo dos Carboidratos/genética , Domínio Catalítico , Pré-Escolar , Dimerização , Modelos Animais de Doenças , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Mutação de Sentido Incorreto , Linhagem , Estabilidade Proteica , Alinhamento de Sequência , Triose-Fosfato Isomerase/genética
20.
Hist Cienc Saude Manguinhos ; 26(1): 245-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30942313

RESUMO

This paper focuses on geneticists Salvador Armendares's and Rubén Lisker's studies from the 1960s to the 1980s, to explore how their work fits into the post-1945 human biological studies, and also how the populations they studied, child and indigenous, can be considered laboratories of knowledge production. This paper describes how populations were considered for different purposes: scientific inquiry, standardization of medical practices, and production or application of medicines. Through the narrative of the different trajectories and collaborations between Armendares and Lisker, this paper also attempts to show the contact of their scientific practices, which brought cytogenetics and population genetics together at the local and global levels from a transnational perspective.


Assuntos
Genética Populacional/história , Genética Humana/história , Povos Indígenas/história , Erros Inatos do Metabolismo dos Carboidratos/história , Criança , Citogenética/história , Deficiência de Glucosefosfato Desidrogenase/história , História do Século XX , Humanos , Povos Indígenas/genética , Cariotipagem/história , Lactase/deficiência , Lactase/história , México
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA