1.Myocardial Layer-Specific Strain Analysis in Children with Mitochondrial Disease
Lucy Youngmin EUN ; Young Mock LEE
Yonsei Medical Journal 2018;59(1):128-134
PURPOSE: Children with mitochondrial disease (MD) have clinical phenotypes that are more severe than those found in adults. In this study, we assessed cardiac function in children with MD using conventional and advanced echocardiographic measurements, explored any unique patterns present, and investigated the development of early cardiomyopathy (CMP). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 33 children with MD. All patients underwent transthoracic echocardiography with conventional and advanced myocardial analysis. We compared all data between patients and an age-matched healthy control group. RESULTS: Conventional echocardiographic diastolic measurements of mitral E, E/A, and tissue Doppler E′ were significantly lower and E/E′ was significantly higher in children with MD, compared with the measurements from the control group. There was no significant difference in longitudinal and radial strain between the groups. Circumferential strain in the endocardium (p=0.161), middle myocardium (p=0.008), and epicardium (p=0.042) were lower in patients, compared to the values in controls. Circumferential strain was correlated with E′ (p < 0.01, r>0.60). CONCLUSION: In children with MD, myocardial circumferential strain may develop early in all three layers, even with normally preserved longitudinal and radial strain. This may be an early diagnostic indicator with which to predict CMP in this patient population.
Biomechanical Phenomena
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Child
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Echocardiography, Doppler
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Female
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Humans
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Male
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Mitochondrial Diseases/diagnostic imaging
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Mitochondrial Diseases/pathology
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Mitochondrial Diseases/physiopathology
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Myocardium/pathology
2.Neurobiology of schizophrenia spectrum disorders: the role of oxidative stress.
Stephen J WOOD ; Murat YÜCEL ; Christos PANTELIS ; Michael BERK
Annals of the Academy of Medicine, Singapore 2009;38(5):396-396
Mitochondrial dysfunction and oxidative stress are increasingly implicated in the pathophysiology of schizophrenia. The brain is the body's highest energy consumer, and the glutathione system is the brain's dominant free radical scavenger. In the current paper, we review the evidence of central and peripheral nervous system anomalies in the oxidative defences of individuals with schizophrenia, principally involving the glutathione system. This is reflected by evidence of the manifold consequences of oxidative stress that include lipid peroxidation, protein carboxylation, DNA damage and apoptosis - all potentially part of the process of neuroprogression in the disorder. Importantly, oxidative stress is amenable to intervention. We consider the clinical potential of some possible interventions that help reduce oxidative stress, via augmentation of the glutathione system, particularly N-acetyl cysteine. We argue that a better understanding of the mechanisms and pathways underlying oxidative stress will assist in developing the therapeutic potential of this area.
Acetylcysteine
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Glutathione
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Humans
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Magnetic Resonance Imaging
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Mitochondrial Diseases
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Nervous System
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physiopathology
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Oxidative Stress
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Schizophrenia
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physiopathology
3.Primary Pulmonary Hypertension as a Manifestation of Adult Multi-System Mitochondrial Disorder.
Yonsei Medical Journal 2009;50(2):307-308
No abstract available.
Aged
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Female
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Humans
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Hypertension, Pulmonary/*etiology
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Mitochondrial Diseases/*complications/*pathology/physiopathology
4.Copy number and deletion of 4 977 bp of granular cell mitochondria DNA in patients with diminished ovarian reserve.
Journal of Central South University(Medical Sciences) 2010;35(8):879-884
OBJECTIVE:
To determine the copy number of granular cell mitochondria DNA (mtDNA) and deletion of 4 977 bp in patients with diminished ovarian reserve (DOR) to primarily study the structural integrity of granular cell mtDNA.
METHODS:
We selected 50 DOR patients and 50 patients with normal ovarian reserve (NOR). Granular cells in liquor folliculi of these patients were collected at ovum pick-up day. DNA was extracted from the granular cells. The mtDNA 4 977 bp deletion of granular cells was detected by PCR and the number of granular cells mtDNA copies was detected by real-time PCR.
RESULTS:
No 4 977 bp deletion of ovary granular cell mitochondria DNA in the 100 patients was detected. There was no significant difference in the relative quantity of granular cell mitochondria DNA in the DOR group and the NOR group.
CONCLUSION
The structure of granular cells mtDNA in DOR patients is complete and granular cells may be used as donor cells for DOR patients plasma autologous transplants mitochondorial.
Adult
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Case-Control Studies
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DNA, Mitochondrial
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genetics
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Female
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Fertilization
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Granulosa Cells
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metabolism
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Humans
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Infertility, Female
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genetics
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Oocytes
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physiology
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Ovarian Diseases
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genetics
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Ovarian Follicle
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cytology
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Ovary
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physiopathology
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Sequence Deletion
5.Clinical and Molecular Characteristics in 100 Chinese Pediatric Patients with m.3243A>G Mutation in Mitochondrial DNA.
Chang-Yu XIA ; Yu LIU ; Hui LIU ; Yan-Chun ZHANG ; Yi-Nan MA ; Yu QI
Chinese Medical Journal 2016;129(16):1945-1949
BACKGROUNDMitochondrial diseases are a group of energy metabolic disorders with multisystem involvements. Variable clinical features present a major challenge in pediatric diagnoses. We summarized the clinical spectrum of m.3243A>G mutation in Chinese pediatric patients, to define the common clinical manifestations and study the correlation between heteroplasmic degree of the mutation and clinical severity of the disease.
METHODSClinical data of one-hundred pediatric patients with symptomatic mitochondrial disease harboring m.3243A>G mutation from 2007 to 2013 were retrospectively reviewed. Detection of m.3243A>G mutation ratio was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Correlation between m.3243A>G mutation ratio and age was evaluated. The differences in clinical symptom frequency of patients with low, middle, and high levels of mutation ratio were analyzed by Chi-square test.
RESULTSSixty-six patients (66%) had suffered a delayed diagnosis for an average of 2 years. The most frequent symptoms were seizures (76%), short stature (73%), elevated plasma lactate (70%), abnormal magnetic resonance imaging/computed tomography (MRI/CT) changes (68%), vomiting (55%), decreased vision (52%), headache (50%), and muscle weakness (48%). The mutation ratio was correlated negatively with onset age (r = -0.470, P < 0.001). Myopathy was more frequent in patients with a high level of mutation ratio. However, patients with a low or middle level of m.3243A>G mutation ratio were more likely to suffer hearing loss, decreased vision, and gastrointestinal disturbance than patients with a high level of mutation ratio.
CONCLUSIONSOur study showed that half of Chinese pediatric patients with m.3243A>G mutation presented seizures, short stature, abnormal MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric patients with these recurrent symptoms should be considered for screening m.3243A>G mutation. Clinical manifestations and laboratory abnormalities should be carefully monitored in patients with this point mutation.
Adolescent ; Age of Onset ; Asian Continental Ancestry Group ; Chi-Square Distribution ; Child ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Female ; Hearing Loss ; pathology ; physiopathology ; Humans ; Infant ; Lactic Acid ; blood ; Magnetic Resonance Imaging ; Male ; Mitochondrial Diseases ; blood ; genetics ; pathology ; physiopathology ; Mutation ; Point Mutation ; genetics ; Polymerase Chain Reaction ; Retrospective Studies ; Seizures ; pathology ; physiopathology
6.Enzyme analysis of isolated mitochondrial respiratory chain complex III deficiency.
Yan-yan MA ; Tong-fei WU ; Yu-peng LIU ; Qiao WANG ; Jin-qing SONG ; Jiang-xi XIAO ; Yu-wu JIANG ; Yan-ling YANG
Chinese Journal of Pediatrics 2011;49(11):848-852
OBJECTIVETo study the clinical and enzymological characteristics of the children with mitochondrial respiratory chain complex III deficiency.
METHODThe clinical manifestations of five patients (3 males, 2 females) were summarized. Spectrophotometric assay was used for the analysis of respiratory chain complex I to V enzyme activity in peripheral blood leukocytes, after obtaining venous blood.
RESULT(1) Five patients were hospitalized at the age of 1 month to 15 years. Three patients had Leigh syndrome with progressive motor developmental delay or regression and weakness. One had severe liver damage and intrahepatic cholestasis. One presented muscle weakness. (2) Deficient complex I + III activity was identified in five patients. Their complex I + III activities in peripheral blood leukocytes were 3.0 to 14.2 nmol/min per mg mitochondrial protein (control: 84.4 ± 28.5 nmol/min per mg mitochondrial protein). The ratio of complex I + III to citrate synthase decreased to 3.5 to 22.9% (normal control 66.1 ± 14.7%). The activities of complex III decreased to 10.4 to 49.3% of the lowest control value, while complex I, II, IV and V activities were normal. The results supported the diagnosis of isolated respiratory chain complex III deficiency.
CONCLUSIONComplex III deficiency is a kind of disorder of energy metabolism with various manifestations. The complex I + III activities and the ratio of complex I + III to citrate synthase were lower than those of the control. The activities of complex I, II, IV and V were normal.
Adolescent ; Child ; Child, Preschool ; Electron Transport Complex I ; metabolism ; Electron Transport Complex II ; metabolism ; Electron Transport Complex III ; metabolism ; Female ; Humans ; Infant ; Leigh Disease ; Leukocytes, Mononuclear ; enzymology ; Male ; Mitochondrial Diseases ; diagnosis ; metabolism ; physiopathology