RESUMO
In the last few years, many studies have pinpointed the crucial role of thyroid hormone (TH) transporters for TH action in human target cells. The importance was better documented by the phenotype observed in patients harboring mutations of the monocarboxylate transporter 8 (MCT8) gene immediately linked to Allan-Herndon-Dudley syndrome, in which severe neurological findings are associated with abnormal TH levels. The hereditary pattern of MCT8 mutations is X chromosome linked, with males presenting a homogeneous neurological psychomotor phenotype and mental retardation associated with low serum thyroxine and elevated triiodothyronine levels. The mechanism of disease is still obscure, and the physiopathology as well as the existent therapeutic options need to be discussed in order to improve the clinical management.
Assuntos
Membrana Celular/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Hormônios Tireóideos/metabolismo , Transporte Biológico , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Hipotonia Muscular/genética , Hipotonia Muscular/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Mutação , FenótipoRESUMO
Central hypotonic is one of the most difficult issues in neurology, ruling out neurogenetic syndromic causes is critical, Prader-Willi syndrome (PWS) it is the most frequent genetic syndrome, it is caused by the loss of expression of the paternal allele in a group of imprinted genes within 15q11-q13, and is characterized by severe prenatal and postnatal hypotonia. SNURF-SNRPN gene methylation detects 99% of the cases but fluorescent in situ hybridization (FISH) analysis is necessary to confirm chromosome microdeletions. The advantage of SNRP-quantitative strategy of methylated alleles is that it makes it possible to make the diagnosis and identify deletions and mosaicism in one reaction. In infants clinical diagnosis is difficult. It has been proposed that around 40% of hypotonic patients have PWS but an accurate percentage has not been established. Twenty-four central hypotonic infants were studied by this molecular strategy, showing 41.5% with the disease. This molecular approach also permitted calculation of gene dosage and detection of those cases with microdeletion.
Assuntos
Metilação de DNA , Hipotonia Muscular/etiologia , Proteínas Centrais de snRNP/genética , Pré-Escolar , Deleção Cromossômica , Diagnóstico Diferencial , Dosagem de Genes , Humanos , Lactente , Recém-Nascido , Hipotonia Muscular/sangue , Hipotonia Muscular/genética , Hipotonia Muscular/metabolismo , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/fisiopatologiaRESUMO
PURPOSE: Symptoms of the gastrointestinal tract, frequent in patients with diabetes mellitus, which may be related to an increase in the production of free radicals, include alterations in the function of the sphincter anal musculature. Such alterations are characterized by a decrease of muscular tone associated with different degrees of fecal incontinence. This study was performed to show the alterations in the anal sphincter pressures of diabetic rats and to evaluate the role of nitric oxide and oxidative stress in this situation. METHODS: Male Wistar rats weighing 250 to 400 g were used. The animals were divided in two groups: control and diabetic. Diabetes was induced through intraperitoneal injection of streptozotocin and the anal pressures were gauged by anorectal manometry. Nitric oxide was evaluated through measures of nitrites and nitrates, and oxidative stress through the technique of chemoluminescence. RESULTS: There was a significant decrease in the sphincter anal pressure of diabetic animals 60 days after induction (P < 0.05). This pressure returned to basal values after administration of a nitric oxide synthase antagonist. The levels of nitrites and nitrates as well as of lipoperoxidation were significantly increased in the diabetic compared with the control group (P < 0.05). CONCLUSIONS: In this study, hyperglycemia of diabetes mellitus caused an increase in the oxidative stress. Apparently the elevation of nitric oxide levels was one of the responsible factors for the decrease of anal sphincter pressures.
Assuntos
Canal Anal/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Hipotonia Muscular/fisiopatologia , Óxido Nítrico/fisiologia , Canal Anal/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Masculino , Manometria , Hipotonia Muscular/metabolismo , Estresse Oxidativo/fisiologia , Pressão , Ratos , Ratos WistarRESUMO
OBJECTIVE: To determine the spectrum of presentation, including both clinical and biochemical abnormalities, and the clinical course in a cohort of patients with complete mitochondrial trifunctional protein (MTP) deficiency, a rare inborn error of mitochondrial fatty acid oxidation. STUDY DESIGN: A questionnaire was sent to the referring physicians from 25 unselected MTP-deficient patients. RESULTS: Twenty-one patients could be included. Questionnaires about four patients were not returned. Nine (43%) patients presented with rapidly progressive clinical deterioration; six (67%) of them had hypoketotic hypoglycemia. The remaining 12 patients presented with a much more insidious disease with nonspecific chronic symptoms, including hypotonia (100%), cardiomyopathy (73%), failure to thrive, or peripheral neuropathy. Ten patients (48%) presented in the neonatal period. Mortality was high (76%), mostly attributable to cardiac involvement. Two patients who were diagnosed prenatally died despite treatment. CONCLUSION: Complete MTP deficiency often presents with nonspecific symptomatology, which makes clinical recognition difficult. Hypotonia and cardiomyopathy are common presenting features, and the differential diagnosis of an infant with these signs should include MTP deficiency. In spite of early diagnosis and treatment, only a few patients with this condition have survived.
Assuntos
Erros Inatos do Metabolismo Lipídico/diagnóstico , Complexos Multienzimáticos/deficiência , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Progressão da Doença , Feminino , Cardiopatias/etiologia , Cardiopatias/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Proteína Mitocondrial Trifuncional , Hipotonia Muscular/etiologia , Hipotonia Muscular/metabolismoRESUMO
Systematic detection of inborn errors of metabolism (IEM) has usually encountered difficulties in developing countries. We present our experience in a high-risk population in Mexico between 1973 and 1998 with particular reference to the last 10 years, during which time infrastructure and support were considerably improved. Only disorders of intermediary metabolism were sought. The total number of patients studied is not available, but in the last 10 years, patients numbered 5,186. Routine metabolic screening was performed on all patients, with additional tests according to the clinical picture and screening results. The referral criteria have increasingly diversified, one-third being neurological conditions. Of the referrals, 33.8% were from pediatricians (31.1% of whom were at critical medicine departments) and the remainder from specialists. The number of diagnosed patients has increased to 1 per 43.9 patients studied. Amino acid defects have been the most prevalent, the proportion of organic acid and carbohydrate disorders having increased in the last 10 years, associated with improved diagnostic facilities. The most frequently diagnosed diseases were PKU, type 1a glycogen storage, and maple syrup urine disease (MSUD), their frequency apparently varying among different regions of Mexico. Other results of our program include training of specialists and technicians, development of the Latin American Metabolic Information Network, a procedure to locally prepare a special food product low in phenylalanine for the treatment of PKU patients, and extension of approaches for these disorders to the investigation metabolic derangements of infant malnutrition. This work demonstrates that inherited metabolic diseases constitute a significant load in pediatric pathology and that their study can and should be pursued in developing nations.