1/68. Nonrandom tissue distribution of mutant mtDNA.Heteroplasmic mitochondrial dna (mtDNA) defects are an important cause of inherited human disease. On a cellular level, the percentage of mutant mtDNA is the principal factor behind the expression of the genetic defect. Marked variation in the level of mutant mtDNA among tissues is thought to be responsible for the diverse clinical phenotypes associated with the same pathogenic mtDNA mutation. This study was designed to determine whether the percentage level of a pathogenic mtDNA molecule is determined by a purely random process. The tissue distribution of the A3243G MELAS point mutation was analyzed in five individuals who were members of a family with maternally inherited diabetes and deafness. The level of mutant mtDNA was measured in four tissues in three individuals and three tissues in two individuals. The highest level of mutant mtDNA occurred in skeletal muscle, followed by hair follicles, and then buccal mucosa, with the lowest levels in blood (leucocyte/platelet fraction). The probability of observing any strict hierarchy in family is 4.82 x 10(-5). These results indicate that the distribution of the A3243G mutation is not solely determined by random processes.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
2/68. prevalence of macular pattern dystrophy in maternally inherited diabetes and deafness. GEDIAM Group.OBJECTIVE: To evaluate the prevalence of macular pattern dystrophy (MPD) in maternally inherited diabetes and deafness (MIDD), a new subtype of diabetes mellitus that cosegregates with a mutation of mitochondrial dna (i.e., the substitution of guanine for adenine at position 3243 of leucine transfer rna) and to report the clinical characteristics of MPD. DESIGN: Prospective cohort study. PARTICIPANTS: Forty-six patients from 29 families with an adenine-to-guanine mutation of mitochondrial dna were recruited from a French collaborative multicenter study. Thirty-five patients had MIDD, 8 were asymptomatic children of MIDD patients, and 3 had melas syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes). The 33 MIDD patients with diabetes were matched for diabetes duration and gender with 33 patients with "common" type-2 diabetes to compare the prevalence of diabetic retinopathy (DR) in both series. methods: All patients had a full ophthalmologic examination and fundus photographs. MAIN OUTCOME MEASURES: The presence and severity of MPD and DR were assessed in each patient. RESULTS: Thirty MIDD patients (85.7%) of 35 exhibited bilateral MPD characterized by linear pigmentation surrounding the macula and optic disc. In 24 of these 30 patients, visual acuity was 20/25 or more in both eyes. The prevalence of DR was 6% in MIDD patients with diabetes versus 15% for patients with common type-2 diabetes (a difference that was not significant, P = 0.23). The fundus of each of the eight asymptomatic children was normal. MPD was present in one of the three cases of MELAS. CONCLUSION: The prevalence of MPD in MIDD is high. Its detection may be helpful for the diagnosis of this new subtype of diabetes, for which specific treatments may be proposed.- - - - - - - - - - ranking = 12keywords = diabetes (Clic here for more details about this article) |
3/68. diabetes mellitus, deafness, muscle weakness and hypocalcemia in a patient with an A3243G mutation of the mitochondrial dna.In a 54-year-old woman with diabetes mellitus, hearing loss, muscle weakness and hypocalcemia, caused by idiopathic hypoparathyroidism, an A to G transition at the nucleotide position of 3243 (A3243G mutation) was found in the mitochondrial dna from her leukocytes. Clinical features of diabetes mellitus and hearing loss in association with the A3243G mutation are compatible with a diagnosis of maternally inherited diabetes and deafness (MIDD). Although hypoparathyroidism is rarely seen in MIDD, we consider that hypoparathyroidism in this patient is a possible phenotype caused by the A3243G mutation of mitochondrial dna.- - - - - - - - - - ranking = 3keywords = diabetes (Clic here for more details about this article) |
4/68. Maternally inherited diabetes and deafness (MIDD): unusual occult exocrine pancreatic manifestation in an affected German family.The mitochondrial (mt) 3243 dna mutation is an underlying cause of maternally inherited diabetes and deafness (MIDD) syndrome and the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We report an affected German MIDD pedigree with maternal lineage over three generations. The index patient, her mother, her maternal aunt and her maternal grandmother all suffered from diabetes and premature hearing loss and were positive on testing for the mt 3243 dna mutation. The 27-year-old index patient had a history of grand mal seizures. As sequela of abdominal ultrasound and confirmed by magnetic resonance cholangio-pancreaticography, she was diagnosed with chronic pancreatitis with pancreatic calcifications and pancreatic duct dilation, although she was completely asymptomatic and with no signs of steatorrhoea. She did not have gallstones and the common bile duct was normal. A possible etiopathogenic pathway for pancreatitis could be a suppressive effect of the mt 3243 mutation on the oxidative phosphorylation in affected mitochondria. Although pancreatitis and pancreatic dysfunction in association with the mt 3243 mutation, especially in patients with comorbidity of MELAS and diabetes, has previously been described as a rare manifestation, this case is specific because of the discrepancy of advanced morphological pancreatic alterations and complete lack of pancreatogenic symptoms.- - - - - - - - - - ranking = 7keywords = diabetes (Clic here for more details about this article) |
5/68. Woodhouse and Sakati syndrome (MIM 241080): report of a new patient.A 32-year-old male with Woodhouse Sakati syndrome (MIM 241080) is described. Two of the proband's brothers also have diabetes mellitus and similar facial features, however they are not dysarthric. An affected older brother died of an unknown cause at age 30. This confirms autosomal recessive inheritance.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
6/68. A DIDMOAD syndrome family with juvenile glaucoma and myopia findings.We present here two DIDMOAD syndrome cases (diabetes mellitus, diabetes insipidus, optic atrophy, deafness) in a Turkish family. In the examination of the propositus who had consanguineous parents, diabetes mellitus, diabetes insipidus, optic atrophy, and deafness were observed in addition to myopia, juvenile glaucoma, posterior polar cataract, and dilatation of the urinary tract. diabetes mellitus, diabetes inspidus, optic atrophy, deafness, myopia, and ventricular septal defect were observed in his elder brother. Juvenile onset diabetes mellitus, congenital glaucoma, deafness, and heart disease were the other remarkable findings observed in relatives to this family. Juvenile glaucoma, posterior polar cataract observed in our propositus, and myopia in both our DIDMOAD syndrome cases are the first ophthalmic manifestations described in the DIDMOAD syndrome.- - - - - - - - - - ranking = 5.5893855522029keywords = diabetes insipidus, diabetes, insipidus (Clic here for more details about this article) |
7/68. Acute lymphoblastic leukemia in one of two siblings with alstrom syndrome.alstrom syndrome is a rare autosomal recessive disease; less than 60 cases have been reported. No Chinese patient with this disease has been reported previously in the literature. Here, we describe an 11-year-old Chinese boy with this condition. His elder sister also had alstrom syndrome, and his father had non-insulin-dependent diabetes mellitus. Both siblings had degenerative retinopathy, obesity, mental retardation, perceptive hearing loss, short stature, non-insulin-dependent diabetes mellitus, nephropathy, hyperlipidemia, acanthosis nigricans, and hepatic dysfunction. The boy also developed acute lymphoblastic leukemia, which was confirmed by cytochemistry and immunophenotyping findings. He received chemotherapy and radiotherapy for the malignancy. The present case suggests that acute lymphoblastic leukemia may be coincident with or may be a previously undescribed systemic manifestation of alstrom syndrome.- - - - - - - - - - ranking = 2keywords = diabetes (Clic here for more details about this article) |
8/68. Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, wolff-parkinson-white syndrome and placenta accreta.Mitochondrial dna (mtDNA) defects are associated with a number of human disorders. Although many occur sporadically, maternal transmission is the hallmark of diseases due to mtDNA point mutations. The same mutation may manifest strikingly different phenotypes; for example, the A to G substitution at np 3243 was first reported in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (the melas syndrome), but is also found in patients with diabetes and deafness. Here we present a case of gestational diabetes, deafness, premature greying, placenta accreta and Wolff-Parkinson-White (WPW) syndrome associated with a mtDNA mutation. Although this is the first report of such an association, study of 27 other patients with WPW syndrome failed to confirm that this mtDNA mutation is a common cause of such pre-excitation disorders.- - - - - - - - - - ranking = 6keywords = diabetes (Clic here for more details about this article) |
9/68. diabetes mellitus and profound insulin resistance in Johanson-Blizzard syndrome.Pancreatic exocrine insufficiency in Johanson-Blizzard syndrome (JBS) is well described but only two previous patient reports document pancreatic endocrine insufficiency manifested as diabetes mellitus, and each patient required only a modest dose of insulin to control hyperglycemia. We report a patient with JBS and new-onset diabetes mellitus with profound insulin resistance, with no clinical or laboratory evidence of pancreatic exocrine insufficiency.- - - - - - - - - - ranking = 2keywords = diabetes (Clic here for more details about this article) |
10/68. alstrom syndrome in two siblings.alstrom syndrome is a very rare autosomal recessive inherited disorder. Only 50 cases have been reported since the syndrome was first described in 1959. This syndrome is characterized by obesity, impaired glucose tolerance with insulin resistance, retinal degeneration, neurosensory deafness, acanthosis nigricans, hepatic dysfunction, and some endocrine disorders. The index case of this report was a 12-year-old girl who became blind at the age of 6 years as the result of progressively impaired vision. At the age of 12, diabetes mellitus was diagnosed and acanthosis nigricans presented in the neck, axilla, and groin regions. Her 10-year-old brother had similar symptoms. electroretinography and audiometry disclosed generalized pigmentary epithelial change, decreased to absent cone and rod responses, and moderate sensorineural hearing loss in both siblings. biochemistry and oral glucose tolerance tests showed diabetes mellitus, dyslipidemia, and hepatic dysfunction in the index case. Elevations of insulin, c-peptide, and leptin concentrations were found in both siblings. insulin resistance was also demonstrated in both siblings using the modified insulin suppression test with constant infusion of somatostatin and exogenous insulin.- - - - - - - - - - ranking = 2keywords = diabetes (Clic here for more details about this article) |
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