RESUMO
Emeritus Professor Edward Alan Glasper from the University of Southampton discusses the complexities of care delivery to children in hospital who have life limiting medical conditions.
Assuntos
Tomada de Decisões/ética , Pediatria/métodos , Assistência Terminal/métodos , Atenção à Saúde/ética , Atenção à Saúde/métodos , Humanos , Lactente , Pseudo-Obstrução Intestinal/mortalidade , Pseudo-Obstrução Intestinal/psicologia , Masculino , Meios de Comunicação de Massa/tendências , Encefalomiopatias Mitocondriais/mortalidade , Encefalomiopatias Mitocondriais/psicologia , Distrofia Muscular Oculofaríngea , Oftalmoplegia/congênitoRESUMO
INTRODUCTION: The Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) disease is an extremely underrated syndrome beginning around the age of eighteen years. Because of its severity, this diagnosis should be considered when a patient presents an atypical anorexia nervosa. MNGIE disease is inherited in an autosomal recessive manner and related to mutations of the TYMP gene (ch22q13.32-qter), encoding the thymidine phosphorylase. The MNGIE is often misdiagnosed and is associated with a time to diagnostic of about 12 years after first symptoms. Thus this critical review aims to help clinicians better identify symptoms and paraclinical markers of the MNGIE as a differential diagnosis of atypical anorexia nervosa. METHODS: A literature search was performed using PubMed and Google Scholar databases. RESULTS: The clinical diagnosis of the MNGIE disease should be based on the association of severe loss of weight and some additional symptoms: (1) severe gastrointestinal dysmotility (nausea, vomiting, intestinal pseudo-obstruction), (2) ptosis or external ophtalmoplegia and (3) peripheral sensorimotor neuropathy. When MNGIE disease is clinically suspected, paraclinical testing can help to validate the MNGIE diagnostic: (1) Arterial blood test reveals lactic acidemia (e.g. an increased serum concentration of lactate without pH modifications), and (2) Brain MRI indicates leukoencephalopathy, usually asymptomatic. Direct evidence of MNGIE disease is based on specific testing of: (1) the thymidine phopshorylase enzyme activity in leukocytes is less than 10% of the control, (2) the increase of plasmatic thymidine (>3µmol/L) and the increase of plamatic deoxyuridine (>5µmol/L), (3) the evidence of mutations of the TYMP gene by molecular genetic testing. CONCLUSION: The MNGIE disease is a severe trouble with multisystemic complications. The thymidine phopshorylase enzyme activity in leukocytes should be measured as soon as possible when a patient presents atypical anorexia nervosa.
Assuntos
Anorexia Nervosa/diagnóstico , Anorexia Nervosa/psicologia , Encefalomiopatias Mitocondriais/diagnóstico , Encefalomiopatias Mitocondriais/psicologia , Adolescente , Idade de Início , Anorexia Nervosa/terapia , Criança , Humanos , Pseudo-Obstrução Intestinal , Encefalomiopatias Mitocondriais/genética , Encefalomiopatias Mitocondriais/terapia , Doenças Raras , Timidina Fosforilase/genéticaRESUMO
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the thymidine phosphorylase gene (ECGF1). We present the first detailed report of a Brazilian MNGIE patient, harboring a novel ECGF1 homozygous mutation (C4202A, leading to a premature stop codon, S471X). Multiple deletions and the T5814C change were found in mitochondrial DNA. Together with gastrointestinal symptoms, endocrine involvement and memory dysfunction, not reported in MNGIE to date, were the most preeminent features.
Assuntos
Transtornos Cognitivos/genética , Gastroenteropatias/genética , Hipogonadismo/genética , Encefalomiopatias Mitocondriais/complicações , Encefalomiopatias Mitocondriais/genética , Mutação/genética , Timidina Fosforilase/genética , Adulto , Encéfalo/enzimologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Brasil , Códon sem Sentido/genética , Transtornos Cognitivos/enzimologia , Transtornos Cognitivos/fisiopatologia , Análise Mutacional de DNA , DNA Mitocondrial/genética , Gastroenteropatias/enzimologia , Gastroenteropatias/fisiopatologia , Deleção de Genes , Marcadores Genéticos/genética , Humanos , Hipogonadismo/enzimologia , Hipogonadismo/fisiopatologia , Masculino , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Encefalomiopatias Mitocondriais/psicologiaRESUMO
We describe two children carrying an inherited T899C mutation in the mitochondrial ATPase 6 gene with mild encephalopathy and normal postnatal growth followed by tall stature and obesity. No familial tall stature, endocrine anomaly or advanced skeletal age were present. Failure to thrive is a characteristic finding in most patients with a mitochondrial disease. Our observations suggest that children with encephalomyopathy, even in the presence of a significant clinical overgrowth, should be screened for a possible defect in oxidative phosphorylation.
Assuntos
Estatura/fisiologia , Encefalomiopatias Mitocondriais/patologia , Obesidade/fisiopatologia , Adolescente , Envelhecimento/fisiologia , Estatura/genética , Criança , DNA Mitocondrial/genética , Feminino , Crescimento/genética , Crescimento/fisiologia , Humanos , Encefalomiopatias Mitocondriais/genética , Encefalomiopatias Mitocondriais/psicologia , Obesidade/etiologia , Obesidade/genética , Mutação Puntual/genéticaRESUMO
Mitochondrial encephalomyopathies (ME) are a multisystemic group of diseases characterized by a wide range of biochemical and genetic mitochondrial defects with a variable mode of inheritance. We studied the neuropsychological profile, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) data in a group of ME patients in order to look for common or specific cognitive defects and a possible correlation with related brain areas. Three main cognitive areas were assessed: general intelligence, memory functions and visuo-perceptual skills. Our sample included 16 ME patients (nine males, seven females) aged 25-68 years (mean age 45.2, SD 13.0). No sign of mental deterioration was found in the group of elderly subjects. Despite subjects showing no global cognitive impairment they scored lower in nonverbal versus verbal tasks. Visuo-spatial skills and short-term memory were selectively impaired. There was no correlation between neuropsychological results and age, illness duration, age of onset, clinical phenotypes, genetic mitochondrial alterations and pharmacological therapy. The most frequent SPECT pattern observed was the hypoperfusion of temporal lobes, with a direct localization in the temporal cortex and with prevalent mesial involvement. The neuropsychological profile and SPECT imaging revealed similarities with focal defects.
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Transtornos Cognitivos/etiologia , Encefalomiopatias Mitocondriais/psicologia , Adulto , Idoso , Feminino , Humanos , Inteligência , Imageamento por Ressonância Magnética , Masculino , Memória , Pessoa de Meia-Idade , Encefalomiopatias Mitocondriais/diagnóstico , Testes Neuropsicológicos , Desempenho Psicomotor , Tomografia Computadorizada de Emissão de Fóton Único , Escalas de WechslerRESUMO
Mothers of children with mitochondrial disorders, inherited neurodegenerative diseases, are faced with a frightening diagnosis and numerous demands associated with caring for these children. The psychological profile of mothers whose children carry a mitochondrial disorder is unknown. Forty-two mothers of children with mitochondrial disorders were interviewed and administered the Minnesota Multiphasic Personality Inventory--Second Edition (MMPI-2). Fifty-six per cent of the mothers had scores in the pathological range on three or more scales, most notably on Hypochondriasis, Hysteria and Paranoia scales. The MMPI-2 profile is associated with situational anxiety and stress or may be associated with carrier status characteristics. Whatever the cause, future studies need to determine whether supportive services can reduce the level of anxiety and stress in mothers of children with these disorders.
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Encefalomiopatias Mitocondriais/psicologia , Miopatias Mitocondriais/psicologia , Relações Mãe-Filho , Mães/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , MMPI , Pessoa de Meia-IdadeRESUMO
Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243(DM-Mt3243) is a new disease. Patients have a distinctly different picture from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). During observations at the Saiseikai Central Hospital, the following findings were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls without family history. DM-Mt3243 patients often need insulin more often than NIDDM controls without family history. Post-treatment neuropathy and insulin edema are often found in DM-Mt3243, and the two phenomena possibly have a similar pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric disorders of functional psychosis are observed frequently in DM-Mt3243. Mild headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormalities such as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme Q may be effective in the relief of these neuromuscular symptoms.