ascorbic-acid and MELAS-Syndrome

This paper briefly summarizes the results of a long-term, open pharmacotherapy trial in 16 patients with well-characterized mitochondrial disease. Outcome measures included repeated clinical evaluation, 31P-NMR spectroscopy and near-infrared spectroscopy. Treated patients appeared to survive longer with less functional disability and medical complications than typically seen in clinical practice.

Topics: Adolescent; Adult; Age of Onset; Antioxidants; Ascorbic Acid; Child; Coenzymes; Female; Humans; Kearns-Sayre Syndrome; Male; MELAS Syndrome; MERRF Syndrome; Methylprednisolone; Middle Aged; Mitochondrial Myopathies; Oxidative Phosphorylation; Oxygen Consumption; Treatment Outcome; Ubiquinone; Vitamin E; Vitamin K; Vitamins

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common subtype of mitochondrial encephalopathy. In the past, it was believed that most hereditary white matter lesions were lysosome storage disorders or peroxisome diseases. However, in recent years, white matter lesions have been increasingly regarded as a common feature of patients with mitochondrial diseases. In addition to stroke-like lesions, about half of the patients with MELAS reported white matter lesions in the brain.. Herein, we provide a case of A 48-year-old female who presented with episodic loss of consciousness with twitching of extremities. Previous medical history revealed 10 years of history of epilepsy, 10 years of history of diabetes, a history of hearing loss, and unknown etiology. Ancillary findings included brain magnetic fluid-attenuated inversion recovery showed symmetrical lesions in the bilateral parietal lobe with high signal intensity at the edge, and high signal intensity in the bilateral occipital lobe, paraventricular white matter, corona radiata, and the center of semiovale.. Mitochondrial deoxyribonucleic acid gene sequencing returned A3243G point mutation and it supports the diagnosis of intracranial hypertension.. Considered the diagnosis of symptomatic epilepsy, the patient was treated with mechanical ventilation, midazolam, and levetiracetam, and the limb twitching symptoms were controlled. The patient was comatose, chronically bedridden, with gastrointestinal dysfunction, and was treated prophylactically with antibiotics against infection, parenteral nutrition, and other supportive measures. B vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone were given, and mechanical ventilation and midazolam were stopped after 8 days. He was discharged from the hospital on 30 days and continued symptomatic treatment with B-vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone, and antiepileptic treatment with levetiracetam, with outpatient follow-up.. No further seizures were recorded and the patient recovered well.. MELAS syndrome without stroke-like episodes of diffuse posterior cerebral white matter lesions is rare in clinical practice, and the possibility of MELAS syndrome should be considered in symmetric posterior cerebral white matter lesions.

Topics: Acidosis, Lactic; Ascorbic Acid; Female; Humans; Leukoencephalopathies; Levetiracetam; Male; MELAS Syndrome; Midazolam; Middle Aged; Stroke; Vitamin E; Vitamins

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are thought to be rarely accompanied by macroangiopathy. We reported a case of MELAS that presented right distal internal carotid arterial (ICA) stenosis and reviewed 12 similar previously reported cases involving intracranial large blood vessels.. A 38-year-old man suffered from recurrent stroke-like episodes (SE) such as alternating hemiparesis (right lesion 3 years ago and current left lesion), cortical blindness and seizure for 3 years, and was previously misdiagnosed as cerebral infarction. Magnetic Resonance Angiography (MRA) and Digital Subtraction Angiography (DSA) revealed right distal ICA stenosis and sparse cortex blood vessels, which were related to the previous SE.. He was diagnosed by genetic screening (a mitochondrial DNA A3243G point mutation) and presence of high lactic acidosis (4.03 mmol/L), which rose to 7.8 mmol/L after exercise.. The patient received Coenzyme Q10, vitamin C, L-arginine for 2 weeks and valproic acid sodium (400 mg bid) to prevent seizures till now.. He is currently less active and intelligent than his peers, with occasional seizures, and needs family care.. Till date, there are 12 reported cases of MELAS combined with major cerebral arteries abnormalities including stenosis, dissection, occlusion, reversible vasoconstriction, aneurysms, and atherosclerosis. Hence, macroangiopathy in MELAS is not very rare. There is correlation between the affected vessels and the lesions in some cases, but not in others, which may increase the misdiagnosis rate. Hence, mitochondrial diseases cannot be excluded due to concurrent macroangiopathic lesions.

Topics: Acidosis, Lactic; Adult; Arginine; Ascorbic Acid; Carotid Stenosis; Humans; Male; MELAS Syndrome; Mitochondrial Encephalomyopathies; Point Mutation; Ubiquinone; Valproic Acid

Mutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Poracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H+/e ratio and lower deltapsi), but had similar CO activity. These results indicate that both substitutions (F263L > A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping.

Topics: Ascorbic Acid; DNA, Mitochondrial; Electron Transport Complex IV; Gene Deletion; Gene Expression; Humans; Kinetics; MELAS Syndrome; Onium Compounds; Optic Atrophies, Hereditary; Organophosphorus Compounds; Paracoccus denitrificans; Proton Pumps; Tetramethylphenylenediamine