Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 9 year-old boy with MELAS. High dosed oral thiamine administration and high fat diet induced remarkable neurological and biochemical improvement. His mother had episodic headaches and hemiplegia, probably MELAS. He complained muscle weakness and repeated episodes of vomiting started from 2 years of age. High levels of serum lactate and pyruvate were recognized, but with no metabolic acidosis. He developed generalized muscle weakness, growth retardation, generalized convulsions and stroke-like episodes at 5 years old. Optic nerve atrophy and mental retardation gradually appeared. A muscle biopsy at 5 years old revealed numerous ragged-red fibers with excess accumulation of lipid droplets and glycogen particles. Scattered fibers had no cytochrome c oxidase (CCO) activity representing focal CCO deficiency. An electron microscopy showed markedly increased number of giant mitochondria filled with markedly proliferated complicated cristae. Pyruvate dehydrogenase complex level in the fibroblasts was within normal ranges. Serum carnitine level was normal. With oral administration of thiamine hydrochloride (1000 mg) and high fat diet (60-70%), muscle weakness improved, and lactate and pyruvate levels in the serum reduced to normal ranges, whereas the mental deterioration, muscle atrophy, pes cavus progressed very slowly. He died from cardiac and renal failures at 9 years old. Autopsied muscles showed a marked decrease in cytochrome c oxidase activity (biochemically 12.8% of the normal level), and almost all muscle fibers had no cytochrome c oxidase activity histochemically. The progression of the MELAS was probably in parallel with the decrease in CCO activity.
 ...
PMID:[A case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with progressive cytochrome c oxidase deficiency]. 255 13

An A to G transition at nucleotide 3,243 in the tRNA(Leu(UUR)) gene of mitochondrial DNA (mtDNA) has been suggested to be the disease-related mutation for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Recently, the same mutation has also been found in several pedigrees with maternally inherited diabetes mellitus and sensorineural deafness. We report here a family showing the association of deafness and diabetes mellitus, as the predominant clinical features, with this mutation. The mutation was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA, in two generations. In this family, it is noteworthy that two members with the mutation had some symptoms of MELAS such as short stature, seizures and mental retardation and that one had no clinical symptoms though the mtDNA mutation was identified in his blood. The findings in this family demonstrate the diversity of clinical expression of the mtDNA mutation and suggest that a combination of sensorineural deafness and diabetes mellitus is only one typical presentation of the various phenotypic features caused by the 3,243 mutation.
 ...
PMID:[Detection of a mutation in mitochondrial DNA in a family with sensorineural deafness and diabetes mellitus as the predominant clinical features]. 756 31

We examined the clinical and biochemical features of 27 cases with acute myoglobinuria who had been suspected of having metabolic myopathies. The systematic biochemical studies included the measurements of 13 glycolytic enzymes, mitochondrial respiratory chain enzymes, carnitine palmitoyltransferase (CPT) and 5 enzymes of fatty acid beta-oxidation. Enzyme defects were found in 9 patients using muscle biopsy specimens: phosphorylase deficiency in 3, CPT deficiency in 4 and phosphoglycerate kinase deficiency in 2. One patient was diagnosed as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with the histopathological examination and clinical data. A suspicion of beta-oxidation disorder was entertained in some patients of which the activities were about 50% of control means. However, no evidence to substantiate its significance as the enzyme defects was obtained from our data. Sixteen of 17 undiagnosed cases could be divided into two groups according to precipitating factors as follows: one had exercise as the factors and the other had infection. These groups also showed some differences in clinical features. In the infection group, myoglobinuria tended to progress more rapidly and was occasionally followed by acute renal failure. And some cases had additional associated conditions such as mental retardation or epilepsy. On the other hand, the exercise group had only myopathic symptoms. The difference in these clinical features between the two groups suggested that they had the different pathogenic mechanisms respectively.
 ...
PMID:[Clinical and biochemical analysis of 27 patients with myoglobinuria of unknown causes]. 778 Dec 10

Lactic acidosis has been associated with a variety of clinical conditions and can be due to mutation in nuclear or mitochondrial genes. We performed mutations screening of all mitochondrial tRNA genes in 44 patients who referred as hyperlactic acidosis. Patients showed heterogeneous phenotypes including Leigh disease in four, MELAS in six, unclassified mitochondrial myopathy in 10, cardiomyopathy in five, MERRF in one, pure lactic acidosis in six, and others in 12 including facio-scaplo-femoral muscular dystrophy (FSFD), familial cerebellar ataxia, recurrent Reye syndrome, cerebral palsy with mental retardation. We measured enzymatic activities of pyruvate dehydrogenase complex, and respiratory chain enzymes. All mitochondrial tRNA genes and known mutation of ATPase 6 were studied by single strand conformation polymorphism (SSCP), automated DNA sequence and PCR-RFLP methods. We have found one patient with PDHC deficiency and six patients with Complex I+IV deficiency, though the most of the patients showed subnormal to deficient state of respiratory chain enzyme activities. We have identified one of the nucleotide changes in 29 patients. Single nucleotide changes in mitochondrial tRNA genes are found in 27 patients and one in ATPase 6 gene in two patients. One of four pathogenic point mutations (A3243G, C3303T, A8348G, and T8993G) was identified in 12 patients who showed the phenotype of Leigh syndrome, MELAS, cardimyopathy and cerebral palsy with epilepsy. Seventeen patients have one of the normal polymorphisms in the mitochondrial tRNA gene reported before. SSCP and PCR-RFLP could detect the heteroplasmic condition when the percentage of mutant up to 5, however, it cannot be observed by direct sequencing method. It is important to screen the mtDNA mutation not only by direct sequence but also by PCR-RFLP and the other sensitive methods to detect the heroplasmy when lactic acidosis has been documented in the patients who are not fulfilled the criteria of mitochondrial disorders.
 ...
PMID:Mitochondrial tRNA gene mutations in patients having mitochondrial disease with lactic acidosis. 1633 22

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare congenital mitochondrial DNA mutation disease. Here, we report a 4-year-old girl, who presented with short stature, mental retardation, and recurrent seizures, underwent simultaneous F-FDG PET/MRI examination. An interesting contradiction images were found on bilateral frontal, left temporal, occipital, and parietal lobes, which were with high blood flow shown on 3D-ASL perfusion images, but low uptake of F-FDG on PET images. The contradiction of high blood flow and low glucose metabolism gave us a clue to make the diagnosis of MELAS. The final diagnosis was MELAS confirmed by genetic testing.
 ...
PMID:Simultaneous 18F-FDG PET/MRI Assists Diagnosis of a Rare Disease, MELAS. 3037 84