Heterogeneous phenotypic manifestations of maternally inherited deafness associated with the mitochondrial A3243G mutation. Case report

Hoptasz, Magdalena; Szczuciński, Adam; Losy, Jacek

doi:10.1016/j.pjnns.2013.12.007

Cited by 6 publications

(5 citation statements)

References 12 publications

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“…A wide range of clinical features can also present, including hearing loss, myopathy, neuropathy, migraine, epilepsy, ataxia, short stature, diabetes mellitus (DM), gastrointestinal disease, and cardiomyopathy. [ 8 9 ] Previous studies have reported a large proportion of death attributable to cardiac causes in MELAS patients. [ 7 ] Isolated MM severely affecting respiratory muscles is an uncommon clinical spectrum of m.3243A>G mitochondrial disease.…”

Section: Linical F Eaturesmentioning

confidence: 99%

“…The first symptoms include exercise intolerance, seizures, paralysis, hemianopsia, mental anomaly, gastrointestinal disorders, respiratory muscles weakness, and arrhythmia. [ 7 8 9 ] Patients with MELAS are usually sent to the emergency room, and are predominantly initially misdiagnosed as myasthenia gravis, epilepsy, cerebral infarction, encephalitis, gastrointestinal diseases, or heart diseases, leading to mistaken treatment and delayed therapeutic opportunity. [ 1 4 7 9 ] Physicians should notice that patients are usually young.…”

Section: Ifferential D Iagnosis and mentioning

confidence: 99%

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Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

Wang

2015

Chinese Medical Journal

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Objective:Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. MELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well.Data Sources:The data used in this review came from published peer review articles from October 1984 to October 2014, which were obtained from PubMed. The search term is “MELAS”.Study Selection:Information selected from those reported studies is mainly based on the progress on clinical features, blood biochemistry, neuroimaging, muscle biopsy, and genetics in diagnosing MELAS.Results:MELAS has a wide heterogeneity in genetics and clinical manifestations. The relationship between mutations and phenotypes remains unclear. Advanced serial functional magnetic resonance imaging (MRI) can provide directional information on this disease. Muscle biopsy has meaningful value in diagnosing MELAS, which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers. Genetic studies have reported that approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial transfer RNA (Leu (UUR)) gene (MT-TL1).Conclusions:MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MRI, muscle biopsy, and genetics.

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Section: Linical F Eaturesmentioning

confidence: 99%

Section: Ifferential D Iagnosis and mentioning

confidence: 99%

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

Wang

2015

Chinese Medical Journal

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“…The decrease in ATP leads to a decrease in contractility and subsequently results in decreased stroke volume. The increase in end diastolic volume and pressure in the left ventricle causes further left ventricular remodeling, most often, left ventricular hypertrophy ( 22 ). Cardiac conductance disorders might occur by a rearrangement of the cardiac conductance system induced by the mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac conductance disorders might occur by a rearrangement of the cardiac conductance system induced by the mitochondrial dysfunction. Common cardiac conduction abnormalities seen in MIDD include Wolff Parkinson White syndrome, frequent ventricular extrasystoles, and atrial fibrillation ( 20 , 22 ). Cardiac conductance disorders might contribute to sudden deaths; therefore, patients diagnosed with MIDD should undergo a comprehensive cardiac examination to avoid adverse outcomes ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients

Yang

et al. 2021

Front. Endocrinol.

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AimsTo investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.MethodsPubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: “Maternally inherited diabetes and deafness” OR “MIDD” OR “Mitochondrial diabetes”. The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.ResultsTotally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes.ConclusionsThe young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.

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“…The annual and lifetime prevalence are 18% and 33% in women, respectively, and 6 and 10% in men. 24 not only the classical MELAS presentation but also MIDD (maternally inherited diabetes mellitus and deafness) 21,38,53 with or without hypertrophic cardiomyopathy and renal failure, CPEO 36,59 and mixed-phenotypes showing a variety of different complaints, signs and symptoms. 81 One explanation for the observed variation in phenotypic expression is "heteroplasmy" where wild-type mitochondrial DNA coexists with mutated molecules in the same cell and different cells have different heteroplasmy percentages.…”

Section: The M3243a>g Mutation Causes a Spectrum Of Disordersmentioning

confidence: 99%

Mitochondrial Migraine: Disentangling the angiopathy paradigm in m.3243A>G patients

Smeitink¹,

Koene²,

Saris³

et al. 2019

JIMD Reports

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Migraine, characterized by recurrent attacks of predominantly unilateral throbbing headache, affects approximately 15% of the adult population and is an important cause of disability worldwide. Knowledge required for the development of new classes of antimigraine drugs might come from studying rare metabolic diseases associated with migraine. An illustrative example of a monogenetic disorder associated with migraine is the spectrum of disorders caused by the m.3243A>G mutation in the mitochondrial transfer RNA Leucine. Reported migraine prevalence figures in patients with this particular mutation vary considerably, but compared to the general population, m.3243A>G patients have a higher migraine prevalence. This burdensome symptom might sometimes even be the only clinical feature in maternal relatives carrying the m.3243A>G mutation. Although the exact sequence of events and the relative importance of factors underlying migraine in m.3243A>G MELAS spectrum disorders are still enigmatic, substantial evidence in man exist that dysfunctional mitochondria in both the vascular, the smooth muscle cells and the neuronal system and the interaction between these are at the starting point of the migraine developing pathophysiological cascade. Exclusively based on results of studies performed in patients harboring the m.3243A>G mutation, either in vivo or ex vivo, we here summarize our current understanding of mitochondrial angiopathy associated migraine in m.3243A>G patients which knowledge might lead to potential new avenues for migraine drug development.

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Heterogeneous phenotypic manifestations of maternally inherited deafness associated with the mitochondrial A3243G mutation. Case report

Cited by 6 publications

References 12 publications

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients

Mitochondrial Migraine: Disentangling the angiopathy paradigm in m.3243A>G patients

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