scholarly journals Case Report: A Variant Non-ketotic Hyperglycinemia With GLRX5 Mutations: Manifestation of Deficiency of Activities of the Respiratory Chain Enzymes

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-xing Feng ◽  
Xiu-wei Zhuo ◽  
Zhi-mei Liu ◽  
Jiu-wei Li ◽  
Wei-hua Zhang ◽  
...  

Objective: Variant non-ketotic hyperglycinaemia (NKH) is a rare disorder characterized by variable clinical, biochemical, and imaging features. The variant form of NKH is rare and characterized by variable clinical, biochemical and imaging features.Subjects: Herein, we report a girl with variant NKH with two mutations in glutaredoxin 5 (GLRX5), which has been described in only three patients.Results: The clinical and biochemical phenotypes of the patient are also described. She suffered from developmental regression associated with spasticity, developmental delay, anemia and optic atrophy. The mitochondrial leukoencephalopathy was used to designate these disorders. An increased T2 signal from the medulla oblongata to the C6 spinal region was also observed on spinal cord MRI. Tandem mass analysis of a dried blood sample revealed elevated levels of glycine. The patient has two compound heterozygous mutations (c.151_153 del AAG and c.196C>T) in the GLRX5 gene. The c.196C>T mutation led to a stop codon (p.Q66Ter). Activities of mitochondrial respiratory chain (MRC) complexes II+III in the patient's fibroblasts were abnormal.Conclusions: We present the case of a girl with variant NKH who manifested spasticity and bilateral cavitating leukoencephalopathy. The patient had a deficiency of a respiratory chain enzyme, and this is the first report. Genetic testing is important for physicians to evaluate suspected variant NKH patients and to provide proper genetic counseling.

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0178125 ◽  
Author(s):  
Michael Nafisinia ◽  
Lisa G. Riley ◽  
Wendy A. Gold ◽  
Kaustuv Bhattacharya ◽  
Carolyn R. Broderick ◽  
...  

2007 ◽  
Vol 377 (1-2) ◽  
pp. 138-143 ◽  
Author(s):  
Santosh B. Shinde ◽  
Vipul C. Save ◽  
Neela D. Patil ◽  
Kaushala P. Mishra ◽  
Anil G. Tendolkar

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1918-1918
Author(s):  
Myung-Geun Shin ◽  
Hyeoung Joon Kim ◽  
Hye-Ran Kim ◽  
Il-Kwon Lee ◽  
Duck Cho ◽  
...  

Abstract Background: Mitochondrial DNA (mtDNA) was particularly susceptible to oxidative damage and mutation because of the high rate of reactive oxygen species (ROS) generation and inefficient mtDNA repair system. Somatic mutations of mtDNA lead to errors in the mtDNA-encoded polypeptide chains belonging to the proton-translocating complexes of the mitochondrial inner membrane. Therefore, we investigated level of ROS, mitochondrial genomic aberrations (mitochondrial genomic instability, mtGI) and the change in enzyme activity of mitochondrial respiratory chain complexes I–IV and in acute myeloid leukemia (AML) cells. Methods: Forty-eight AML bone marrow samples and 57 control blood samples were used after receiving informed consent. The intracellular ROS generation of cells can be investigated using the 2′,7′-dichlorfl uorescein-diacetate and flow cytometry. The results were expressed as mean fluorescence intensity (MFI). We sequenced the mtDNA control region, the tRNA leucine 1 gene plus part of NADH dehydrogenase (ND) 1, and cytochrome b (CYTB) directly and checked the activity of mitochondrial respiratory chain enzyme complexes I to IV using a spectrophotometric kinetic assay. To investigate mtGI, we also examined six mtGI repeats (303 poly C, 16184 poly C, 514CA repeats, 3566 poly C, 12385 poly C and 12418 poly A) using size-based PCR product separation with capillary electrophoresis. mtGI was further confirmed by cloning and sequencing. The mtDNA molecules were analyzed quantitatively using real-time PCR. Results: MFI in AML cells (4,435±709) was significantly higher than those in control blood cells (1,562±141) (P<0.05). Many polymorphisms, as well as new mtDNA variants in the control region and ND1 and CYTB genes were detected in this study. A total of 606 mtDNA sequence variants were identified. Of these, 15 mtDNA variants were identified as novel mutations that were absent from control subjects and established mtDNA polymorphism databases. There were profound alterations of mtGI in the 303 poly C, 16184 poly C, and 514 CA repeats. Seven patients (15%) had leukemia cell-specific mtDNA substitution mutations in the ND1 and CYTB genes. The enzyme activities of AML cells compared with control subjects were 0.828±2.72 vs. −2.48±3.18 for complex I, 0.03±0.08 vs. 0.144±1.72 for complex II/III, and 0.244±0.16 vs. 0.505±0.73 for complex IV. The AML cells showed decreased enzyme activity in respiratory chain complexes I, II, and III. The AML cells had an approximately two-fold decrease in mtDNA copy number compared with the results for control subjects. Conclusion: Mitochondrial genomic aberrations were commonly observed in primary AML cells. High level of ROS in these cells might be an injury to the mitochondrial genome. These mtDNA alterations may impair the activity of mitochondrial respiratory chain enzyme complexes and reduce the mtDNA copy number in patients with AML.


2020 ◽  
pp. jclinpath-2020-206801
Author(s):  
Atsuhito Takeda ◽  
Kei Murayama ◽  
Yasushi Okazaki ◽  
Atsuko Imai-Okazaki ◽  
Akira Ohtake ◽  
...  

AimsMitochondrial cardiomyopathy (MCM) is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in the pathology examination. We aim to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders.MethodsQuantitative analysis of mitochondria using electron microscopy and immunohistopathological analysis with respiratory chain enzyme antibodies were performed in 11 patients with hypertrophic or restrictive cardiomyopathy who underwent endomyocardial biopsy for possible MCM . Respiratory chain enzymatic assay in biopsied myocardium and genetic studies were also performed in all the subjects to define MCM.ResultsFour patients were diagnosed with MCM according to the recent criteria of mitochondrial respiratory chain disorders. Using electron microscopy with quantitative analysis, the volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared with the non-MCM group (p=0.007). Immunohistopathological results were compatible with the result of the respiratory chain enzymatic assay.ConclusionsPathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody.


2019 ◽  
Vol 2 (31) ◽  
pp. 16-19
Author(s):  
L. G. Mishura ◽  
L. B. Gaikovaya ◽  
G. G. Rodionov ◽  
V. A. Dadali

Mitochondrial respiratory chain enzyme activities were determined by spectrophotometric enzyme assay in lymphocytes of 100 patients with acute myocardial infarction. A significant decrease in the activity of complexes II–III and IV and an increase in the activity of complex I of the respiratory chain were found. According to the correlation analysis, the feedback of troponin T and I concentrations in the serum and the activity of complex IV of the respiratory chain was detected. A decrease in the activity of the IV complex of the mitochondrial lymphocyte respiratory chain below 2.87 IU/g of protein indicates an increased level of clinical risk in patients with acute myocardial infarction.


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