Inherited Metabolic Disorders and Stroke Part 1

Testai, Fernando D.; Gorelick, Philip B.

doi:10.1001/archneurol.2009.309

Cited by 78 publications

(25 citation statements)

References 38 publications

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“…“ M itochondrial E ncephalomyopathy, L actic A cidosis, and at least one S troke‐like episode,” is the typical “MELAS” syndrome with underlying m.3243A>G mutation . However, phenotypic presentation can vary, even in patients carrying the same mutation.…”

Section: Resultsmentioning

confidence: 99%

“…It is an acronym for M itochondrial E ncephalomyopathy, L actic A cidosis, and at least one S troke‐like episode. In about 80% of patients, it is caused by a maternally transmitted mutation m.3243A>G in the mitochondrial tRNA leucine 1 (MT‐TL1) . The highest prevalence of the “MELAS” mutation ( m.3243A>G ) is estimated to be 7.59 per 100 000 persons in northeast England, 16.3 per 100 000 in northern Finland, and 236 per 100 000 in Australia.…”

Section: Introductionmentioning

confidence: 99%

“…In about 80% of patients, it is caused by a maternally transmitted mutation m.3243A>G in the mitochondrial tRNA leucine 1 (MT-TL1). 1,2 The highest prevalence of the "MELAS" mutation (m.3243A>G) is estimated to be 7.59 per 100 000 persons in northeast England, 16.3 per 100 000 in northern Finland, and 236 per 100 000 in Australia. So far, no correlation to ethnic origin has been described.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial DNA mutation “m.3243A>G”—Heterogeneous clinical picture for cardiologists (“m.3243A>G”: A phenotypic chameleon)

Niedermayr

Pölzl

Scholl‐Bürgi

et al. 2018

Congenital Heart Disease

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Cardiac manifestation can encompass hypertrophic or dilated cardiomyopathy, as well as preexcitation syndromes or conduction delay. In general, the clinical presentation to meet the "MELAS" criteria varies due to heteroplasmy. Thus, cardiologists should screen patients with unexplained cardiac features in the context of deafness, short stature and learning disabilities for mtDNA mutations, especially the m.3243A>G mutation. A clear diagnosis is essential as a basis for prognostic advice concerning the disease course and clinical impact on family testing.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitochondrial DNA mutation “m.3243A>G”—Heterogeneous clinical picture for cardiologists (“m.3243A>G”: A phenotypic chameleon)

Niedermayr

Pölzl

Scholl‐Bürgi

et al. 2018

Congenital Heart Disease

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“…Acute oxidative phosphorylation (Figure 9) defect may have a crucial role in the pathophysiology of stroke-like episodes. The transfer RNA of leucine mtDNA mutation decreases protein synthesis and causes oxidative phosphorylation failure, leading ultimately to adenosine triphosphate depletion and energy failure [38, 39]. Low level of low-density leucine, isoleucine, and valine (Figure 10) is a characteristic of the plasma of stroke patients [40].…”

Section: Resultsmentioning

confidence: 99%

A Two-Level Model for the Analysis of Syndrome of Acute Ischemic Stroke: From Diagnostic Model to Molecular Mechanism

Dai

Zhang

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Prompt and accurate diagnosis of acute ischemic stroke is critical to seek acute therapy. In traditional Chinese medicine (TCM) science, there is a comprehensive system of diagnosis and medical care of acute ischemic stroke. Here we introduce a two-level model for the analysis of TCM syndrome of acute ischemic stroke. Owing to the limitation of sample size and imbalance, we focused on the analysis of wind-phlegm collateral obstruction syndrome (Feng Tan Yu Zu Zheng). Firstly, a Support-Vector-Machine- (SVM-) based diagnostic model was set up through selection of core symptoms. After pairwise undersampling, we improved the performance of prediction and generated the core symptoms-based diagnostic model of wind-phlegm collateral obstruction syndrome. Next, Pathway Pattern-based method and MetaDrug platform were used to shed light on the molecular basis of the significance of core symptoms in three complementary aspects: symptom-gene-pathway multilayer correlation network, enriched pathways, and most relevant interaction network. The integration of diagnostic model and molecular mechanism analysis creates an interesting perspective for better understanding the syndrome. The two-level model would provide a new opportunity for the study of TCM syndromes.

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“…Patients with migraine, short stature, and strokes that do not respect vascular territories should be investigated with CSF and serum studies, particularly looking for increased lactate and pyruvate. A high lactate:pyruvate ratio is consistent with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes; diagnosis is made through skeletal muscle biopsy demonstrating ragged red fibers, and genetic testing should examine for mutations in the mitochondrial DNA genes, MT-TL1 (~80% of cases) or MT-ND5 (Figure 7) [117]. APP duplications or mutations should be screened for if the EOD syndrome is associated with lobar hemorrhages (that is, cerebral amyloid angiopathy).…”

Section: Diagnostic Process and Genetic Testingmentioning

confidence: 99%

Early-onset dementias: diagnostic and etiological considerations

Masellis

Sherborn

Rosa‐Neto

et al. 2013

Alzheimers Res Ther

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This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect.

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Inherited Metabolic Disorders and Stroke Part 1

Cited by 78 publications

References 38 publications

Mitochondrial DNA mutation “m.3243A>G”—Heterogeneous clinical picture for cardiologists (“m.3243A>G”: A phenotypic chameleon)

Mitochondrial DNA mutation “m.3243A>G”—Heterogeneous clinical picture for cardiologists (“m.3243A>G”: A phenotypic chameleon)

A Two-Level Model for the Analysis of Syndrome of Acute Ischemic Stroke: From Diagnostic Model to Molecular Mechanism

Early-onset dementias: diagnostic and etiological considerations

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