Background
Mitochondrial diseases are a group of rare inborn metabolic disorders with multi-systemic manifestations. MTO1 gene mutations are associated with MTO1 (Mitochondrial tRNA Translation Optimization 1) protein deficiency, a mitochondrial disorder, which commonly presents with lactic acidosis and hypertrophic cardiomyopathy.
Case presentation
The authors describe two siblings with mitochondrial cytopathy and distinct outcomes. The index case, a female born in 1989, presented hypotonia and lactic acidosis since birth. She developed a severe myoclonic encephalopathy, movement disorder and psychomotor and growth delay. Respiratory chain enzyme complex measurement in muscle revealed a partial deficiency of complex III and IV. Throughout the years she had multiple decompensations with severe acidemia and died at age of 16, due to a respiratory infection. She never presented cardiac alterations. The younger sibling, a male born in 2002, had a less severe clinical presentation. He presented hypotonia and lactic acidosis at birth. Metabolic study performed in the first days of life revealed elevated plasma alanine and hyperlactacidemia. At 8 months of age a partial deficiency of complex IV was reported. He had a mild persistent hyperlactacidemia, psychomotor development delay, generalized hypotonia, dilated cardiomyopathy and epilepsy. In 2017, at 15 years of age, a genetic study confirmed the mitochondrial disease with identification of two MTO1 likely pathogenic variants [c.413delT (p.M138Sfs*6) / c.1450C > T (p.R484W)]. Currently, he is clinically stable, maintaining a multidisciplinary follow up. The same genotype was confirmed in his sister’s stored DNA.
Conclusions
With this case, report the authors emphasize mitochondrial diseases' phenotypic heterogeneity, even in the same family, and the significance of the new genetic diagnostic techniques. The authors also report a novel MTO1 likely pathogenic variant not described to date.
Idiopathic dilatation of the right atrium is a rare congenital anomaly that presents as an isolated enlargement of the right atrium. Thrombus formation and atrial arrhythmias are the major complications and management with antiplatelet therapy is recommended. Reduction atrial plasty is reserved for specific patients. We report a case of idiopathic dilatation of the right atrium diagnosed prenatally with a 10-year follow-up.
PurposeThis study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features.MethodsIn this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley–Smith formula.ResultsGrade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema.ConclusionHF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT 40155531.
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