Mitochondrial encephalomyopathy is a multisystemic metabolic disorder caused by mutations in mitochondrial or nuclear genes. It commonly presents with stroke-like episodes or myopathy as initial symptoms. This paper reports a young male patient with mitochondrial encephalomyopathy whose early and prominent clinical manifestation was refractory shock, without typical neurological symptoms. The patient initially presented with abdominal pain and lower limb weakness, followed by severe hypotension requiring high-dose vasopressors to maintain blood pressure. His lactate level peaked at 20 mmol/L. After 10 days of symptomatic and supportive treatment, his hypotension resolved; lactate levels returned to normal by day 22. One month later, he still had difficulty weaning from mechanical ventilation and exhibited persistent limb weakness. Genetic testing of the biceps brachii revealed an m.3271T>C mutation in the mitochondrial tRNA gene. Mitochondrial encephalomyopathy may initially present with severe circulatory dysfunction. In patients with lactic acidosis not related to hypoperfusion, mitochondrial disease should be considered, and genetic testing of muscle or other peripheral tissues may improve diagnostic yield.
Humans ; Male ; Mitochondrial Encephalomyopathies/genetics* ; Mutation ; Shock/etiology*

Mitochondrial neurogastrointestinal encephalomyopathy(MNGIE),a rare mitochondrial disorder caused by TYMP gene mutations,is characterized by severe gastrointestinal dysmotility,peripheral neuropathy,and leukodystrophy.This article summarizes the clinical data and intestinal ultrasound findings of a MNGIE case,aiming to provide insights for clinical diagnosis and treatment.
Humans ; Mitochondrial Encephalomyopathies/diagnostic imaging* ; Ultrasonography ; Intestines/diagnostic imaging* ; Male ; Female ; Intestinal Pseudo-Obstruction/diagnostic imaging* ; Ophthalmoplegia/congenital* ; Muscular Dystrophy, Oculopharyngeal

Humans ; Stroke ; MELAS Syndrome

OBJECTIVE: To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia. METHODS: Clinical examinations and laboratory testing were carried out for the patient. The proband and the parents' genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing. Candidate variant was validated by Sanger sequencing. RESULTS: The 1-year-and-8-month-old boy manifested motor developmental delay, ataxia, hypomyotonia, increased serum creatine kinase. Cranial MRI showed cerebellar atrophy with progressive aggravation. Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene, namely c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile), which were respectively inherited from his mother and father. The former was unreported previously and was predicted to be likely pathogenic, whilst the latter has been reported previously and was predicted to be of uncertain significance. CONCLUSION The compound heterozygous c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile) variants probably underlay the disease in the proband. Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.
Ataxia/genetics* ; Atrophy/genetics* ; Cell Cycle Proteins/genetics* ; Child ; Cytoskeletal Proteins/genetics* ; Humans ; Infant ; Male ; Mitochondrial Myopathies ; Mutation ; Neurodegenerative Diseases ; Whole Exome Sequencing

OBJECTIVE: Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation. METHODS: The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed. RESULTS: This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy. CONCLUSION The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.
Acidosis, Lactic ; Adult ; Child ; DNA, Mitochondrial/genetics* ; Humans ; Male ; Mitochondrial Encephalomyopathies ; Mutation ; Stroke ; Young Adult

BACKGROUND/OBJECTIVES: The NAD+ precursor nicotinamide riboside (NR) is a type of vitamin B3 found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; 250 µM) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR (10 µM and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor γ coactivator-1α, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.
Adiponectin ; alpha-2-HS-Glycoprotein ; Alzheimer Disease ; Animals ; Beer ; Carnitine O-Palmitoyltransferase ; Cell Survival ; Cytokines ; DNA, Mitochondrial ; Fatty Liver ; Gene Expression ; Hearing Loss ; Hepatocytes ; Inflammation ; Interleukin-6 ; Mice ; Milk ; Mitochondria ; Mitochondrial Myopathies ; Niacin ; Niacinamide ; Obesity ; Organelle Biogenesis ; Palmitic Acid ; Peroxisomes ; Sirtuin 1 ; Sirtuins ; Transcription Factors ; Tumor Necrosis Factor-alpha

No abstract available.
Biopsy ; MELAS Syndrome

No abstract available.
Biopsy ; MELAS Syndrome

Anticonvulsants ; therapeutic use ; Clonazepam ; therapeutic use ; Female ; Humans ; Levetiracetam ; therapeutic use ; MERRF Syndrome ; drug therapy ; Male ; Myoclonus ; drug therapy

DNA, Mitochondrial ; genetics ; Humans ; MELAS Syndrome ; diagnosis ; diagnostic imaging ; genetics ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; genetics