Case report Adult, isolated respiratory chain complex IV deficiency with minimal manifestations

Finsterer, Josef; Kovács, Gábor G.; Rauschka, Helmut; Ahting, Uwe

doi:10.5114/fn.2015.52412

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…In our protocol, we performed a target genetic analysis before muscle biopsy. However, our protocol could lead to missed mitochondrial myopathies, which can present with isolated hyperCKemia, 53,54 or atypical inflammatory myopathies, such as anti–3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCR) myopathy, which can be present with an asymptomatic elevation of CK for several years before the appearance of weakness 55 . Therefore, we believe that a muscle biopsy should always be performed in unsolved cases or to confirm new pathogenic variants or validate candidate genes 56 …”

Section: Discussionmentioning

confidence: 99%

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

et al. 2021

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Introduction/Aims: Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition. Methods: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement. All patients underwent a neurological examination and nerve conduction and electromyography studies. The first step of the investigation included a screening for Pompe disease. We then evaluated the patients for myotonic dystrophy type II-related CCTG expansion and excluded patients with copy number variations in the DMD gene. Subsequently, the undiagnosed patients were investigated using a target gene panel that included 20 genes associated with isolated hyperCKemia.Results: Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings.Discussion: We have described our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening, and first-line genetic investigations, followed by successive targeted sequencing panels. Both clinical signs and electromyographic abnormalities are associated with increased diagnostic yields.

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Section: Discussionmentioning

confidence: 99%

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

et al. 2021

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“…Bi-allelic loss of function variants in the COX20 (c.41A>G or c.157+3G>C) gene perturbs the assembly of complex IV, which leads to mitochondrial bioenergetic failure, resulting in ataxia and autosomal recessive sensory neuronopathies (Otero et al, 2018 ; Dong et al, 2021 ). Except for COX20, defects or mutations in other CIV assembly proteins such as SURF1, COA3, COA7, and SCO2 may impair axonal transport or mitochondrial copper homeostasis, as well as increase ROS damage, resulting in peripheral neuropathies (Echaniz-Laguna et al, 2013 ; Ostergaard et al, 2015 ; Higuchi et al, 2018 ; Rebelo et al, 2018 ; Finsterer and Winklehner, 2021 ). Mutations in these assembly factors, which are involved in the biogenesis of CIV, LRPPRC (p.Y172C), COX10, SURF1 (834G→A or 820-824dupTACAT), COX15, TACO1, and PET100 (c.3G>C), have been identified in patients with LS (Bugiani, 2005 ; Tay et al, 2005 ; Coenen et al, 2006 ; Weraarpachai et al, 2009 ; Lim et al, 2014 ; Kotecha and Kairamkonda, 2019 ).…”

Section: Dysregulation Of Mitochondrial Bioenergeticsmentioning

confidence: 99%

“…Furthermore, a mutation in the FASTKD2 (fas activated serine-threonine kinase domain 2) gene induces the occurrence of epilepsy in infancy (Ghezzi et al, 2008 ). Patients with bradykinesia and cognitive impairment have a homozygous mutation in PET117, a potential complex IV assembly component (Renkema et al, 2017 ; Finsterer and Winklehner, 2021 ).…”

Section: Dysregulation Of Mitochondrial Bioenergeticsmentioning

confidence: 99%

Mitochondrial protein dysfunction in pathogenesis of neurological diseases

Wang

Zhou

et al. 2022

Front. Mol. Neurosci.

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Mitochondria are essential organelles for neuronal function and cell survival. Besides the well-known bioenergetics, additional mitochondrial roles in calcium signaling, lipid biogenesis, regulation of reactive oxygen species, and apoptosis are pivotal in diverse cellular processes. The mitochondrial proteome encompasses about 1,500 proteins encoded by both the nuclear DNA and the maternally inherited mitochondrial DNA. Mutations in the nuclear or mitochondrial genome, or combinations of both, can result in mitochondrial protein deficiencies and mitochondrial malfunction. Therefore, mitochondrial quality control by proteins involved in various surveillance mechanisms is critical for neuronal integrity and viability. Abnormal proteins involved in mitochondrial bioenergetics, dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance have been linked to the pathogenesis of a number of neurological diseases. The goal of this review is to give an overview of these pathways and to summarize the interconnections between mitochondrial protein dysfunction and neurological diseases.

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Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

Koit

Shevchuk

Ounpuu

et al. 2017

Oxidative Medicine and Cellular Longevity

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We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome. The main rate-controlling steps in HBC are complex IV and adenine nucleotide transporter, but in HCC, complexes I and III. Our kinetic measurements confirmed previous studies that respiratory chain complexes I and III in HBC and HCC can be assembled into supercomplexes with a possible partial addition from the complex IV pool. Therefore, the kinetic method can be a useful addition in studying supercomplexes in cell lines or human samples. In addition, when results from culture cells were compared to those from clinical samples, clear differences were present, but we also detected two different types of mitochondria within clinical HBC samples, possibly linked to two-compartment metabolism. Taken together, our data show that mitochondrial respiration and regulation of mitochondrial membrane permeability have substantial differences between these two cancer types when compared to each other to their adjacent healthy tissue or to respective cell cultures.

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Case report Adult, isolated respiratory chain complex IV deficiency with minimal manifestations

Cited by 4 publications

References 31 publications

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

Mitochondrial protein dysfunction in pathogenesis of neurological diseases

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

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