Teste Repositóri
2014-01-01
Resultados de pesquisa
Foram encontrados 48 registos.
The focus of this chapter is to review the clinical and molecular etiologies of nuclear defects
involved in mtDNA stability and in mitochondrial protein synthesis. The overview done
here will hopefully provide insights towards best diagnostic strategies of mitochondrial
cross–talk disorders, being useful for clinicians when facing similar cases. Additionally we
will present a diagnostic algorithm for these diseases based on our knowledge.
RESUMO
Nos últimos 30 anos, um largo espectro
de doenças multissistémicas associadas
a disfunções da mitocôndria,
designando-se globalmente de citopatias
mitocondriais, têm sido referenciadas,
com sintomatologia desde o período neonatal
até à idade adulta. Estas disfunções
podem afectar qualquer órgão ou tecido
do organismo, embora os músculos esquelético
e cardíaco, e o SNC sejam os
mais afectados, devido à sua elevada
dependência do metabolismo energético.
Há mais de uma década que a investigação
molecular em patologias humanas
relacionadas com disfunções da mitocôndria,
tem sido centralizada no DNA mitocondrial
(mtDNA) embora nos últimos
anos, o foco da atenção se tenha voltado
para a pesquisa de mutações no DNA nuclear
(nDNA).
Objectivos: O principal objectivo
deste estudo foi investigar ao nível
molecular (m...
RESUMO
Objectivos: Avaliar o contributo do
diagnóstico precoce na redução da pesada
morbilidade e mortalidade que se
associa aos defeitos da B-oxidação mitocondrial
dos ácidos gordos.
Método: Avaliação clínica e bioquímica
retrospectiva dos doentes com
defeitos da B-oxidação mitocondrial dos
ácidos gordos (défice em desidrogenases
dos ácidos gordos de cadeia média
- MCAD, défice em desidrogenases dos
ácidos gordos de cadeia longa - LCHAD
e défice múltiplo das desidrogenases dos
ácidos gordos - MADD), diagnosticados
de forma assintomática pelo rastreio metabólico
neonatal alargado, ou diagnosticados
préviamente em fase sintomática.
Registou-se idade de diagnóstico e de
início de tratamento, primeiros sintomas,
clínica à data de diagnóstico, descompensações
e evolução.
Resultados: Foram identificados e
incluídos 1...
Mitochondrial DNA (mtDNA) disorders are an important group of genetic diseases presenting with a multifacet array of clinical manifestations. Highly energy-dependent tissues such as central nervous system and skeletal and cardiac muscles are commonly involved either as multisystem or as isolated organ disease. Characteristic symptoms include epilepsy, myopathy, deafness and ophthalmoplegia, all associated with point mutations in the mtDNA. Pathogenic mtDNA mutations can be heteroplasmic or homoplasmic. Heteroplasmic mutations are typically associated with mutations in mt-tRNA genes. Mutations in mt-tRNAs genes are responsible for the majority of the presentations of a mitochondrial disease being associated with marked clinical heterogeneity. Although tRNA-encoding genes make up only 9% of the entire mitochondrial genome, over 40% of a...
In Portugal the screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) was begun towards the end of 1979, and by 1990 59 cases of PKU and 227 cases of CH had been detected. The early initiation of treatment and the observed mental and motor development, point towards a normal development in these children. A trial screen for congenital adrenal hyperplasia was carried out in 100.000 newborns, from which it was concluded that, under the present conditions, screening at a national level is not justified. A similar study is currently being undertaken for biotinidase deficiency and cystic fibrosis. The results ares discussed, as are the cost/benefits evaluations.
To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort
The understanding of the molecular genetics in sensorineural hearing loss (SNHL) has advanced rapidly during the last decade, but the molecular etiology of hearing impairment in the Portuguese population has not been investigated thoroughly. To provide appropriate genetic testing and counseling to families, we analyzed the whole mitochondrial genome in 95 unrelated children with SNHL (53 nonsyndromic and 42 syndromic) and searched for variations in two frequent genes, GJB2 and GJB6, in the non- syndromic patients. Mutations in mtDNA were detected in 4.2% of the cases, including a hitherto undescribed change in the mtDNA-tRNATrp gene (namely, m.5558A>G). We also identified mono- or biallelic GJB2 mutations in 20 of 53 non-syndromic cases and also detected two novel mutations (p.P70R and p.R127QfsX84). Our data further reinforce the noti...
Medium and short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a rare cause of impaired mitochondrial
fatty acid oxidation. We present a case report of a patient with hyperinsulinism and homozygosity for a
novel mutation causing a kinetic variant of the enzyme. The diagnosis was initially inferred by abnormal
newborn screening acylcarnitine analysis with elevated C4-hydroxyacylcarnitine.
Following a screening on EMS-induced Drosophila mutants defective for formation and morphogenesis of
epithelial cells, we have identified three lethal mutants defective for the production of embryonic cuticle.
The mutants are allelic to the CG12140 gene, the fly homologue of electron transfer flavoprotein:ubiquinone
oxidoreductase (ETF:QO). In humans, inherited defects in this inner membrane protein account for multiple
acyl-CoA dehydrogenase deficiency (MADD), a metabolic disease of β-oxidation, with a broad range of clinical
phenotypes, varying from embryonic lethal to mild forms. The three mutant alleles carried distinct missense
mutations in ETF:QO (G65E, A68V and S104F) and maternal mutant embryos for ETF:QO showed lethal
morphogenetic defects and a significant induction of apoptosis following germ-band elongation. This phe...
