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Acute Respiratory Failure Is the Initial Manifestation in the Adult-Onset A3243G tRNALeu mtDNA Mutation: A Case Report and the Literature Review.

ABSTRACT: Isolated mitochondrial myopathy refers to the condition of mitochondrial disorders that primarily affect the skeletal muscle system. Here we report on a case of a patient who presented with acute respiratory failure as the initial and predominant clinical manifestation after using anesthetic drugs. The diagnosis of mitochondrial myopathy was made by histochemical findings of ragged red fibers with a modified Gomori trichrome Stain in the skeletal muscle biopsy and the genetic detection of an A3243G point mutation in the tRNA^Leu (UUR) gene of mitochondrial DNA (mtDNA) in a peripheral blood specimen. The patient revealed a benign clinical outcome with ventilator assistance and a cocktail treatment. Further, we performed a literature review on patients with respiratory failure as the early and predominant manifestation in adult-onset isolated mitochondrial myopathy. Eleven cases in nine studies (including our case) have been reported, and five of whom underwent DNA analysis all harbored the A3243G mutation in the tRNA^Leu gene of the mtDNA. Use of sedative drugs tends to induce acute respiratory failure in such cases.

SUBMITTER: Pan X

PROVIDER: S-EPMC6657224 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Acute Respiratory Failure Is the Initial Manifestation in the Adult-Onset A3243G tRNALeu mtDNA Mutation: A Case Report and the Literature Review.

Pan Xiaoli X Wang Lijun L Fei Guoqiang G Dong Jihong J Zhong Chunjiu C Lu Jiahong J Jin Lirong L

Frontiers in neurology 20190718

Isolated mitochondrial myopathy refers to the condition of mitochondrial disorders that primarily affect the skeletal muscle system. Here we report on a case of a patient who presented with acute respiratory failure as the initial and predominant clinical manifestation after using anesthetic drugs. The diagnosis of mitochondrial myopathy was made by histochemical findings of ragged red fibers with a modified Gomori trichrome Stain in the skeletal muscle biopsy and the genetic detection of an A32 ...[more]

PMID: 31379729

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Project description:IntroductionMegalosplenia in newly diagnosed multiple myeloma (MM) is extremely rare, posing diagnostic and therapeutic challenges due to its unusual location and clinical manifestations and lack of optimal therapeutic strategies.Case presentationA 65-year-old female who was previously healthy presented with a history of ecchymosis on her right leg accompanied by progressive fatigue for 2 weeks. She was admitted to our center in July 2019 due to thrombocytopenia. The patient presented with megalosplenia, anemia, monoclonal protein (λ-light chain type) in the serum and urine, and 45.6% malignant plasma cells in the bone marrow. Splenectomy was performed due to persistent splenomegaly after 3 cycles of the bortezomib plus dexamethasone regimen, and immunohistochemistry results indicated λ-plasmacytoma of the spleen. The same cytogenetic and molecular abnormalities, including t(14;16), 14q32 amplification, 16q32 amplification, 20q12 amplification, and a novel CYLD gene mutation, were identified using fluorescence in situ hybridization and next-generation sequencing in both bone marrow and spleen samples. Therefore, a diagnosis of MM (λ-light chain type, DS III, ISS III, R-ISS III, high-risk) with spleen infiltration was proposed. The patient did not achieve remission after induction treatment with bortezomib plus lenalidomide and dexamethasone or salvage therapy with daratumumab plus ixazomib and dexamethasone. However, she ultimately did achieve very good partial remission with a regimen of bendamustine plus lenalidomide and dexamethasone. Unfortunately, she died of pneumonia associated with chemotherapy.ConclusionTo our knowledge, only 8 cases of spleen plasmacytoma at MM diagnosis have been described previously. Extramedullary myeloma patients with spleen involvement at diagnosis are younger and that the condition is usually accompanied by splenic rupture with aggressive clinical features and poor prognosis. Further studies are needed to explore pathogenesis and effective therapies to prolong the survival of such patients.

Project description:PurposeThe mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities.MethodsWe present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing.ResultsFive patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm2, the average endothelial cell size was 442 ± 103 μm2 and the average central corneal thickness (CCT) was 551 ± 33 μm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity.ConclusionsIn patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.

Project description:BackgroundSandhoff disease (SD) is an autosomal recessive lysosomal storage disorder, resulting in accumulation of GM2 ganglioside, particular in neuronal cells. The disorder is caused by deficiency of β-hexosaminidase B (HEX-B), due to pathogenic variant of human HEXB gene.MethodThis study describes clinical features, biochemical, and genetic defects among Thai patients with infantile SD during 2008-2019.ResultsFive unrelated Thai patients presenting with developmental regression, axial hypotonia, seizures, exaggerated startle response to noise, and macular cherry red spot were confirmed to have infantile SD based on deficient HEX enzyme activities and biallelic variants of the HEXB gene. In addition, an uncommon presenting feature, cardiac defect, was observed in one patient. All the patients died in their early childhood. Plasma total HEX and HEX-B activities were severely deficient. Sequencing analysis of HEXB gene identified two variants including c.1652G>A (p.Cys551Tyr) and a novel variant of c.761T>C (p.Leu254Ser), in 90 and 10% of the mutant alleles found, respectively. The results from in silico analysis using multiple bioinformatics tools were in agreement that the p.Cys551Tyr and the p.Leu254Ser are likely pathogenic variants. Molecular modelling suggested that the Cys551Tyr disrupt disulfide bond, leading to protein destabilization while the Leu254Ser resulted in change of secondary structure from helix to coil and disturbing conformation of the active site of the enzyme. Genome-wide SNP array analysis showed no significant relatedness between the five affected individuals. These two variants were not present in control individuals. The prevalence of infantile SD in Thai population is estimated 1 in 1,458,521 and carrier frequency at 1 in 604.ConclusionThe study suggests that SD likely represents the most common subtype of rare infantile GM2 gangliosidosis identified among Thai patients. We firstly described a potential common variant in HEXB in Thai patients with infantile onset SD. The data can aid a rapid molecular confirmation of infantile SD starting with the hotspot variant and the use of expanded carrier testing.

Dataset Information

Acute Respiratory Failure Is the Initial Manifestation in the Adult-Onset A3243G tRNALeu mtDNA Mutation: A Case Report and the Literature Review.

Publications

Acute Respiratory Failure Is the Initial Manifestation in the Adult-Onset A3243G tRNALeu mtDNA Mutation: A Case Report and the Literature Review.

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