MITOCHONDRIAL neurogastrointestinal encephalomyopathy is an autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase gene leads to MITOCHONDRIAL genomic dysfunction. Herein, we report a 29-year-old Iranian man with abdominal pain, diarrhea, hearing loss, ophthalmoplegia, sensorimotor axonal neuropathy, and elevated muscle enzymes. Magnetic resonance imaging showed leukoencephalopathic changes. Metabolite analysis revealed a very high thymidine concentration in the patient's urine consistent with the diagnosis of MITOCHONDRIAL neurogastrointestinal encephalomyopathy.

Background: MITOCHONDRIAL myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a progressive maternally inherited multi-organ disorder caused by a mutation in a MITOCHONDRIAL gene. In this disorder recurrent migraine headache, seizure, cerebral insults causing hemiparesis, hemianopia, progressive hearing loss and cognitive problems may occur.Case presentation: The patient is a 12-year girl manifested with malaise, tonic-clonic convulsion and unilateral weakness in left upper and lower extremities. Her problem was begun with seizure, headache and recurrent vomiting, 5 months before the admission. On clinical examination cerebrovascular events was diagnosed. On broader diagnostic studies, also a genetic mutation in A3243G gene, as a definite characteristic for the establishment of the disease, was detected by muscle biopsy.Conclusion: Patients suffering from the syndrome gradually display delayed motor and cognitive development. Therapeutic management of the disease consists of administration of multi-vitamins and coenzyme supplementations, and lowering the serum lactate level using dichloroacetate.

Background: MITOCHONDRIAL ENCEPHALOMYOPATHIES encompass a group of neurologic degenerative disease that occurs due to MITOCHONDRIAL metabolism disorders.Materials and methods: During a two-year period (September 1999-August 2001), 62 patients with the probable diagnosis of MITOCHONDRIAL disorders who have been admitted in neurology department of Mofid children's Hospital were evaluated for clinical and paraclinical findings. Results: The study population included 36 boys and 26 girls, with the mean age of 39.6±37.8 months. Thirty-seven cases became symptomatic during the first 12-month of their life. No triggering factor was found in 43 cases, however, infections were the most common triggering factor in the remainders and were established in 10. The most frequent neurologic findings were developmental regression (87.5%), seizure (72.6%), and abnormal tone (71%). The major biochemical findings were blood lactate elevation in 58 and blood ammonia elevation in 21. The most common neuroimaging findings were brain atrophy (66.1 %), white matter involvement (45.1%), and symmetric bilateral basal ganglia necrosis (33.9%). Leigh syndrome was by far the most prevalent specific syndrome that was observed in 15 patients. Young age of onset and the appearance of developmental arrest or regression has shown to be statistically significant. Conclusion: MITOCHONDRIAL ENCEPHALOMYOPATHIES have a wide range of neurologic manifestations. Blood lactate level is a valuable test in whom the diagnosis is uncertain.

Our body’s nucleated cells contain 500-2000 mitochondria. In the liver mitochondria are specialized to detoxify ammonia in urea cycle, mitochondria are also required, for neurotransmitter metabolism. MITOCHONDRIAL ENCEPHALOMYOPATHIES are genetically, biochemically and clinically heterogeneous group of disorders associated with abnormalities of oxidative phosphorylation.The final diagnosis relied on clinical and molecular criteria. Diagnostic criteria for pediatric MITOCHONDRIAL disorders have been modified from an adult classification system. This criterion is the modified walker criteria. Because MITOCHONDRIAL disease have a natural history of heterogenous groups of disorders, the modified walker criteria is useful to evaluate the major clinical findings of infants and children with diagnosis of MITOCHONDRIAL diseases. By using the modified walker criteria, we are able to gather a large group of pediatric patients with a definite diagnosis of a MITOCHONDRIAL disorder and study their clinical histories.

Alzheimer’s Disease (AD) is the most common form of dementia in the elderly in which an interplay between genes and the environment is supposed to be involved. Mutations in MITOCHONDRIAL DNA (mtDNA) have been suspected to be causally related since MITOCHONDRIAL DNA is maternally inherited in a non-Mendelian way. All MITOCHONDRIAL tRNA genes of 24 AD patients and 50 healthy controls were investigated by sequencing method. Fifteen variations were found in different MITOCHONDRIAL tRNA genes. Eleven variations were polymorphic mutations. Four variations {C1631A, T1633A (tRNA Val), T14704C and T14723C (tRNA Glu)} filled the criteria for pathogenicity of mutation because of their: a) heteroplasmic state, b) conserved nucleotide, c) absence in the literature and d) absence in healthy controls. A12308G polymorphic mutation (tRNA Leu (CUN)) was found in 8 patients. This mutation has been reported in different neurodegenerative diseases as well as controls. We believe that these variations may have pathogenic effects in AD or have secondary effects in the disease process. The percentage of hetroplasmy may play a role in signs/symptoms or onset age of the disease.

When we talk about MITOCHONDRIAL diseases, we refer to the most ubiquitous of metabolic disorders, with pathogenic MITOCHONDRIAL DNA mutation being found in at least 1 in 8000 individuals.The following statement reveals very vividly, the true nature of MITOCHONDRIAL disease, “MITOCHONDRIAL disease may cause any symptom in any tissue at any age by any inheritance (A. Munics).In view of the presence of mitochondria which are essential organelles of nearly all cells, with the exception of mature erythrocyte. MITOCHONDRIAL diseases may affect any organ system and for this reason are now called “MITOCHONDRIAL cytopathies”.

MITOCHONDRIAL cytopathies are clinically and biochemically heterogeneous disorders affecting energy production. Because of the heterogeneity of disorders, the large number of biochemical and genetic defects, and wide spectrum of clinical course, there are limited data about proven effective therapies. Overall, treatments for MITOCHONDRIAL cytopathies are intended to augment energy production and reduce the production of free radicals and other toxic metabolites that further limit the generation of cellular energy. Treatment can be aimed at increasing respiratory chain activity by supplementing relative deficiencies of cofactors required for proper functioning. Possible strategies to consider may include dietary management, supplemental vitamins and cofactors, and specific medications aimed at a particular symptom.The clinical benefits for cofactor and vitamin therapy can include improved strength and endurance, although patients report a variety of benefits. Coenzyme Q10 can be given at dosages ranging from 5 to15 mg/kg/d in two to three divided doses. Levocarnitine is advocated at dosages of 30 mg/kg/d in two to three divided doses. Riboflavin (vitamin B2) at dosages of 100 to 400 mg/d has been shown to be beneficial in some patients. The use of creatine has been shown to improve strength in patients with MITOCHONDRIAL myopathies, although its long-term use should be consider with caution Because of the potential for renal toxicity. The use of antioxidants. (<-lipoic acid, vitamin E, vitamin C, ®-carotene, selenium, vitamin K and N-acetylcysteine) to lessen free radical damage to the MITOCHONDRIAL membrane has a scientific rationale, but again proof of effectiveness does not exist.