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

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

Adult ; Humans ; Language ; MELAS Syndrome ; diagnostic imaging ; physiopathology ; Male ; White Matter ; diagnostic imaging ; physiopathology

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ± standard deviation, 2.79 ± 1.47 vs. 3.83 ± 1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.
Acidosis, Lactic ; drug therapy ; mortality ; Adolescent ; Anticonvulsants ; therapeutic use ; Carbamazepine ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Lamotrigine ; therapeutic use ; Levetiracetam ; administration & dosage ; therapeutic use ; Male ; Mitochondrial Encephalomyopathies ; drug therapy ; mortality ; Oxcarbazepine ; therapeutic use ; Prospective Studies ; Retrospective Studies ; Stroke ; drug therapy ; mortality ; Topiramate ; therapeutic use ; Valproic Acid ; therapeutic use

Adult ; DNA, Mitochondrial ; genetics ; Electroencephalography ; Humans ; MERRF Syndrome ; genetics ; Male ; Mitochondrial Myopathies ; genetics ; Mutation ; RNA, Transfer, Asn ; genetics