Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular diagnosis for mitochondrial diseases offers a powerful means to clarify that mitochondrial DNA (mtDNA) defects have different characteristics from those of nuclear DNA. Regarding the relationship between genotype and phenotype, there is a dual heterogeneity. It means that one mutation, for example, a 3243 mutation, has several clinical phenotypes, including MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), myopathy only, diabetes and/or deafness and even CPEO (chronic progressive external ophthalmoplegia). Conversely, one phenotype, for instance, MELAS has several genetypes; 3243, 3271, and 3291 mutations. The second unique event in mitochondrial DNA mutation is heterogenous distribution of mutant mtDNA in a mitochondrion or a cell that is called heteroplasmy. The extend of heteroplasmy seems different from tissue to tissue providing clues to explain the variability of tissue impairment and heterogenous clinical symptoms. The above evidence suggests that we should take care in selecting tissues to be tested. The third problem remained is on maternal inheritance. It makes the genetic counselling on mitochondrial diseases at clinics difficult and laborious. In conclusion, mtDNA analysis must be used as a last resort to get final diagnosis.
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PMID:[Mitochondrial encephalomyopathies: 3243 mutation as a central matter]. 875 18

A mitochondrial A 3243 G mutation in the tRNA(Leu(UUR)) gene was first described as a common cause of MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome). This same mutation is also the cause of a totally different disorder, a subtype of diabetes mellitus which is inherited maternally and often associated with sensorineural hearing loss. In this paper, we report on a Japanese boy with A 3243 G who developed a previously undescribed combination of symptoms, nephropathy and growth hormone deficiency. The patient first presented with short stature and moderate mental retardation. Growth hormone (GH) provocation tests showed deficient growth hormone secretion. During the course of follow up, he presented with progressive nephropathy followed by the development of diabetes mellitus. The results of laboratory tests and renal biopsy were against incidental association of known types of nephropathy. On PCR-RFLP analysis, the percentage of mutated mtDNA was higher in the renal biopsy specimen than 12 peripheral blood leucocytes. Our case suggests that mitochondrial diseases should be taken into account when there is nephropathy of unknown cause. In addition, the presence of growth hormone deficiency may account for part of the mechanism leading to short stature commonly seen in these patients.
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PMID:Nephropathy and growth hormone deficiency in a patient with mitochondrial tRNA(Leu(UUR)) mutation. 881 55

We studied the prevalence of mitochondrial gene mutations in subjects with insulin-dependent diabetes mellitus (IDDM) in a Chinese population living in Taiwan. Eighty-four subjects with insulin-dependent diabetes mellitus and 105 unrelated normal controls were recruited in the present study. Both an A-to-G mutation at position 3243 and a mutation at position 8,344 of the mitochondrial DNA were screened by polymerase chain reaction-restriction fragment length polymorphism methods and confirmed by direct DNA sequence analysis. The insulin secretory response was assessed by the C-peptide response to glucagon administration. Among 84 IDDM patients, two (2.4%) subjects were found to carry the 3,243 nucleotide pair (np) mutation. There was no np 8,344 mutation in this series. Of the two subjects carrying a mitochondrial gene mutation, case 1 manifested initially as gestational diabetes mellitus. Manifestation of case 2 was consistent with MELAS, a syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The pancreatic beta cell reserve was reduced, as the glucagon-stimulated C-peptide response was very low in these two cases. HLA genotyping studies revealed that case 2 carried DRB1*0301-DQA1*0501-DQB*0201/ DRB1*0405-DQA1*0301-DQB1*0302, which was the most susceptible genotype to IDDM in our population. Anti-GAD65 antibody was also positive in this patient. In addition to the nuclear genes, a defective mitochondrial gene might contribute to some of the clinical cases with IDDM.
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PMID:Mitochondrial gene mutations in patients with insulin-dependent diabetes mellitus in Taiwan. 883 Mar 30

An A-to-G mutation at np3243 in tRNA(Leu) (UUR) gene of the mitochondrial DNA has been described to associate with diabetes mellitus. This exists within the sequence that is important for binding termination factor, which ends the transcription of one of the two major transcripts. We investigated the prevalence of this mutation in randomly selected 276 NIDDM+ 24 IGT, 94 IDDM, and 115 non-diabetic control subjects. The mutation was also reported to exist frequently in slowly progressive IDDM. We recruited 116 juvenile onset autoimmune Type 1 diabetes and 154 autoimmune thyroid diseases to see if this mutation is involved in autoimmunity. We identified this mutation in 3 of 300 NIDDM+IGT (1%). None from IDDM or control group, nor from autoimmune disease group had this mutation. The patients with this mutation did not have cerebro-muscular symptoms as were observed in MELAS. One patient had only slight glucose intolerance indicating diabetes with this mutation may have various phenotypes. Genetic area around tRNA(Leu) (UUR) is a hot spot for pathological mutations. We directly sequenced this area of mtDNA from diabetes and identified a new polymorphism in ND-1 gene, which is situated downstream of tRNALeu (UUR) gene. We screened 154 IDDM and 254 NIDDM+ IGT patients, and identified it in 3 NIDDM and 2 IGT subjects. Both of the NIDDM patients had bilateral hearing impairment. None from 207 non-diabetic control subjects and IDDM were positive for this mutation. Its prevalence was a little more than that of an A-G mutation at np3243.
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PMID:Mitochondrial gene mutations that affect the binding of the termination factor and their prevalence among Japanese diabetes mellitus. 884 39

The clinical relevance of neurological disorders associated with impaired glucose tolerance(IGT) is reviewed. In this review some neurological diseases, such as, myotonic dystrophy, Crow-Fukase syndrome, Wolfram syndrome (DIDMOAD), Friedreich ataxia, spinal muscular atrophy of the Kennedy-Alter-Sung type, amyotrophic lateral sclerosis, Parkinson-dementia, and MELAS are discussed in relation to, glucose intolerance. Although the etiology of these disorders still remains an enigma, MELAS was caused by an A-to-G mutation at nucleotide position 3243 of the mitochondria genome. An association of "diabetic neuropathy" with IGT appears to be negative. Peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio of R-R interval was significantly more common in IGT than in control subjects. In conclusion, diabetes, but not IGT, is associated with peripheral nerve dysfunction.
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PMID:[Neurological disorders associated with impaired glucose tolerance]. 891 31

MELAS is a major maternally inherited mitochondrial (mt) encephalomyopathy of which 80% of cases are associated with mtDNA point mutation (mtDNA 3243, A-->G transition) which exists under heteroplasmic conditions with wild-type mtDNA. The origin of this mutation remains obscure in the reported pedigrees. I analyzed this mutation in a Japanese MELAS pedigree by PCR. The proband had typical MELAS features. The proband's mother was oligosymptomatic (fatigability, nerve deafness and diabetes mellitus). The proband's maternal grandmother was diagnosed as having senile dementia of the Alzheimer type clinically. The brother of the proband's mother was healthy. The ratios of this mutation in muscle and leukocytes of the proband and his mother were 89%, 36%, 79% and 10%, respectively. There were no mutations in muscle and leukocytes of the proband's maternal grandmother and his mother's brother. These results showed the possibility that this mutation occurred in the proband's mother.
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PMID:Did de novo MELAS common mitochondrial DNA point mutation (mtDNA 3243, A-->G transition) occur in the mother of a proband of a Japanese MELAS pedigree? 892 2

Diabetes mellitus associated with 3243 mitochondrial tRNA(Leu(UUR)) mutation (DM-Mt3243) is a subtype of the mitochondrial multisystem syndromes, usually lacking myopathy. Muscle biopsies were obtained from 5 patients with diabetes and one patient with impaired glucose tolerance, all possessing the 3243 mutation without hallmarks of MELAS. The specimens were subjected to histochemical, biochemical, and genetic analysis. Ragged-red fibers were seen in 4 of the 6 patients (67%), and focal cytochrome c oxidase deficiency in 3 (50%). Strongly succinate dehydrogenase-reactive blood vessels was found in 5 patients (83%). The histochemical signs were present even when the mutant percentage was very low. The percentage of mutant DNA was almost always higher in muscles than in leukocytes. The combination of allele specific PCR amplification and PCR-RFLP method was useful to evaluate the mutant proportion. The mutant percentage in muscle was under 50% in 5 (83%) patients. Mitochondrial enzyme activity was deficient only in one patient. This study presents the detailed muscle histopathology in the DM-Mt3243 group. Abnormal histopathologic findings seemed similar to those noted in MELAS. However, mutant percentage in muscles was lower than that of MELAS, and respiratory chain enzyme activity was well preserved.
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PMID:Muscle histopathology in diabetes mellitus associated with mitochondrial tRNA(Leu(UUR)) mutation at position 3243. 907 28

A mitochondrial tRNALeu(UUR) mutation at nucleotide 3,243 is known to be found in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) and has also been identified in several families with maternally inherited diabetes mellitus and hearing loss. We report here audiologic features in patients with hearing loss associated with the mutation. Four patients without and five with MELAS were studied. Most of the patients had bilateral progressive sensorineural hearing loss. The most common shape of the audiogram was sloping, while cases in the advanced stages had flat audiograms. Speech discrimination scores were generally poor and did not parallel the degree of hearing loss. The present study suggests that the lesion for hearing loss could include both cochlear and retrocochlear involvement, but does not demonstrate a significant difference in the audiologic findings between patients with and without MELAS.
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PMID:Audiologic findings in patients with a point mutation at nucleotide 3,243 of mitochondrial DNA. 910 27

We report a 47-year-old female patient showing clinical features of chronic progressive external ophthalmoplegia (CPEO) without stroke-like episodes. Large scale deletion of mitochondrial DNA (mtDNA) was not found in her biopsied muscle, whereas the A-->G transition at position 3243 (A3243G) was detected. The patient's mother had diabetes mellitus, suggesting maternal inheritance. This mutation is usually associated with MELAS, but wide clinical variety of the mutation has been recognized. Although several patients of CPEO with A3243G mutation (CPEO3243) have been found in the Western countries, only one case has been reported in detail in Japan. The CPEO3243 patients, including ours, show retinopathy less frequently, but diabetes mellitus and hearing loss more frequently than CPEO patients with deletions of mtDNA (CPEO delta). CPEO3243 is usually inherited maternally, but almost all CPEO delta is sporadic. With regard to COX activity of biopsied muscles, CPEO3243 resembles CPEO delta more than MELAS3243. This suggests that how the mutant mtDNA is distributed among cells or tissues may have more significant effect on clinical phenotype than what type of mtDNA mutation exists. The presence of such a CPEO3243 patient like ours could be an important suggestion toward further understanding of mitochondrial diseases.
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PMID:[A case of mitochondrial encephalomyopathy showing ophthalmoplegia, diabetes mellitus and hearing loss associated with the A3243G mutation of mitochondrial DNA]. 924 43

Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243(DM-Mt3243) is a new disease. Patients have a distinctly different picture from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). During observations at the Saiseikai Central Hospital, the following findings were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls without family history. DM-Mt3243 patients often need insulin more often than NIDDM controls without family history. Post-treatment neuropathy and insulin edema are often found in DM-Mt3243, and the two phenomena possibly have a similar pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric disorders of functional psychosis are observed frequently in DM-Mt3243. Mild headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormalities such as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme Q may be effective in the relief of these neuromuscular symptoms.
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PMID:Diabetes mellitus associated with 3243 mitochondrial tRNA(Leu(UUR)) mutation: clinical features and coenzyme Q10 treatment. 926 20


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