Pancreatic beta-cell secretory defect associated with mitochondrial point mutation of the tRNALEU(UUR) gene: a study in seven families with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)

Abstract

Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNA(LEU(UUR)) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

An Autopsy Case of Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes Syndrome with Chronic Renal Failure.

“…However,neither of these reports (7)(8)(9)(10)(11)(12)(17)(18)(19) confirmed the presence of abnormal mitochondria in the glomeruli or tubules. The present case thus appears to be the first of MELAS with numerous abnormal mitochondria in podocytes and tubules confirmed by electron microscopy.…”

“…Renal involvement associated with mitochondrial encephalomyopathies has been described in clinical symptomatology, biopsy and molecular genetic studies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), but only a few cases with chronic renal failure have been reported, and detailed pathological studies of such cases are scarce. Wereport here an autopsy case of MELAS syndromewith chronic renal failure.…”

The effects of coenzyme Q 10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation

“…Total DNA was isolated from blood and skeletal muscle. A 427 bp fragment encompassing the tRNA LEU(UUR) mutation site located at nucleotide 3,243 was amplified by modified PCR using [a-32 P]-dATP (1.7 Ci × mmol ±1 ) with forward primer 5 ¢-AAGGTTCGTTTGTTCAACGA (3,029±3,048) and reverse primer 5 ¢AGCGAAGGGTTGTA-GTAGCC (3,437±3,456) [17]. The radioactive fragment was digested with Apa1 for 1 h at 37°C and then followed by electrophoresis on a 5 % non-denaturing polyacrylamide gel.…”

An Autopsy Case of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) with Intestinal Bleeding in Chronic Renal Failure

“…[5][6][7] However, only a few cases with CRF have been reported. 10,11 At autopsy, our patient showed glomerulosclerosis and interstitial fibrosis consistent with ESRD, though there was no direct evidence of mitochondrial abnormality such as enlarged mitochondria with complex cristae in kidney; however, we diagnosed this case as mitochondrial kidney disease diagnosed from the symptoms of multiple organ dysfunction syndrome. Moreover, only a few reports confirmed the presence of abnormal mitochondria in the glomeruli.…”