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1.
Brain ; 146(8): 3470-3483, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454683

RESUMO

Distal hereditary motor neuropathy represents a group of motor inherited neuropathies leading to distal weakness. We report a family of two brothers and a sister affected by distal hereditary motor neuropathy in whom a homozygous variant c.3G>T (p.1Met?) was identified in the COQ7 gene. This gene encodes a protein required for coenzyme Q10 biosynthesis, a component of the respiratory chain in mitochondria. Mutations of COQ7 were previously associated with severe multi-organ disorders characterized by early childhood onset and developmental delay. Using patient blood samples and fibroblasts derived from a skin biopsy, we investigated the pathogenicity of the variant of unknown significance c.3G>T (p.1Met?) in the COQ7 gene and the effect of coenzyme Q10 supplementation in vitro. We showed that this variation leads to a severe decrease in COQ7 protein levels in the patient's fibroblasts, resulting in a decrease in coenzyme Q10 production and in the accumulation of 6-demethoxycoenzyme Q10, the COQ7 substrate. Interestingly, such accumulation was also found in the patient's plasma. Normal coenzyme Q10 and 6-demethoxycoenzyme Q10 levels were restored in vitro by using the coenzyme Q10 precursor 2,4-dihydroxybenzoic acid, thus bypassing the COQ7 requirement. Coenzyme Q10 biosynthesis deficiency is known to impair the mitochondrial respiratory chain. Seahorse experiments showed that the patient's cells mainly rely on glycolysis to maintain sufficient ATP production. Consistently, the replacement of glucose by galactose in the culture medium of these cells reduced their proliferation rate. Interestingly, normal proliferation was restored by coenzyme Q10 supplementation of the culture medium, suggesting a therapeutic avenue for these patients. Altogether, we have identified the first example of recessive distal hereditary motor neuropathy caused by a homozygous variation in the COQ7 gene, which should thus be included in the gene panels used to diagnose peripheral inherited neuropathies. Furthermore, 6-demethoxycoenzyme Q10 accumulation in the blood can be used to confirm the pathogenic nature of the mutation. Finally, supplementation with coenzyme Q10 or derivatives should be considered to prevent the progression of COQ7-related peripheral inherited neuropathy in diagnosed patients.


Assuntos
Doenças Mitocondriais , Ubiquinona , Masculino , Humanos , Pré-Escolar , Ubiquinona/uso terapêutico , Mutação/genética , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/genética , Ataxia/genética
2.
Eur Neurol ; 50(4): 207-14, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14634264

RESUMO

UNLABELLED: The frequency and impact of in-patient assessment by a neurologist in the emergency room (ER) setting remain largely underestimated. The objective of our study was to analyse the impact of neurologist in-patient management. METHODS: Over a period of 12 months, we prospectively recorded the demographics of patients requiring examination in the ER, the ER team's tentative neurological diagnosis, the neurology team's final diagnosis and patient outcomes. The time interval between admission, call for a neurologist and the assessment by the neurologist were recorded. RESULTS: Assessments by neurologists were performed in 14.7% (1,679/11,421) of all patients admitted to the ER. The mean time between admission and examination was 32 (+/- 36) min, irrespective of the day of the week, and dependent on the tentative diagnosis: shorter for stroke and status epilepticus (p < 0.05) and longer for confusion and vertigo (p < 0.05). The initial causes for examination were: stroke (33.1%), epilepsy (20%), loss of consciousness (9%), headaches (9%), confusion (5.4%), peripheral nervous system disorders (4.4%), vertigo (4.2%), cognitive dysfunctions (4%), gait disorders (3.2%) and miscellaneous (7.1%). Overall, false positive or negative diagnoses were produced by the ER in 37.3 and 36.6% of ER admissions, respectively. A complete change of diagnosis by the neurologist was found in 52.5% of patients. Of the patients undergoing a neurological examination, 18.4% were able to go home, 31.8% were admitted to the stroke unit, 32.4% to the general neurology unit and 17.4% to other departments. CONCLUSION: Our study stresses the need for a neurologist in the ER, both in quantitative terms and for the benefit of patient management.


Assuntos
Serviços Médicos de Emergência , Neurologia , Avaliação de Resultados em Cuidados de Saúde , Encefalopatias/terapia , Demografia , Serviços Médicos de Emergência/provisão & distribuição , Serviço Hospitalar de Emergência , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Masculino , Exame Neurológico , Fatores de Tempo , Resultado do Tratamento , Recursos Humanos
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