RESUMO
A case of maternally inherited diabetes and deafness (MIDD)-associated macular pattern dystrophy with a 15-year follow-up is reported. On initial examination at age 37, visual acuity was normal, but chorioretinal atrophy at the posterior pole was already present in both eyes. At age 52, visual acuity remained normal in the right eye and was only slightly decreased in the left eye despite notable extension of the areas of chorioretinal atrophy in that eye. No evidence of diabetic retinopathy was present at any time. This case shows that visual acuity can remain stable in the long term despite extensive lesions of macular pattern dystrophy.
Assuntos
Surdez/genética , Diabetes Mellitus/genética , Degeneração Macular/patologia , Adulto , Diabetes Mellitus/patologia , Diabetes Mellitus/fisiopatologia , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Angiofluoresceinografia , Humanos , Degeneração Macular/fisiopatologia , Masculino , Mutação , Acuidade VisualRESUMO
INTRODUCTION: Laminopathies (diseases related to A/C mutations of lamines) are rare genetic diseases with an extensive phenotypic spectrum, including lipodystrophic syndromes-characterized by a selective loss of adipose tissue-of which the partial Dunnigan family type is the most frequent. CASE REPORT: We report on a 55-year-old woman with diabetes and long-term disabling myalgia. Her cushingoid morphotype, associated with cutaneous lipo-atrophy and muscle hypertrophy in addition to a genetic heritage, led us to the diagnosis of complex partial familial lipodystrophy heterozygous LMNA_c.82C>T, p.Arg28Trp mutation. CONCLUSION: Familial partial lipodystrophic syndromes may have varied phenotypes, mainly cardio-metabolic, which could mimic a particularly severe type 2 diabetes. The diagnostic work-up of this disease has to include a careful investigation of gait troubles and paroxysmal conduction that could lead to sudden death, as well as a genetic examination. In some cases, recombinant leptin can be proposed.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Lamina Tipo A/genética , Lipodistrofia Parcial Familiar/diagnóstico , Lipodistrofia Parcial Familiar/genética , Substituição de Aminoácidos , Diabetes Mellitus Tipo 2/complicações , Diagnóstico Diferencial , Feminino , Heterozigoto , Humanos , Resistência à Insulina/genética , Lipodistrofia Parcial Familiar/complicações , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , FenótipoRESUMO
Mitochondrial diabetes affects up to 1% of patients with diabetes and is often unrecognised by the physicians. Maternally inherited diabetes and deafness (MIDD) resulting from the mutation 3243A>G of the mitochondrial DNA is the most frequent mutation associated with mitochondrial diabetes. This review summarizes the range of clinical phenotypes associated with MIDD and outlines the advances in genetic diagnosis, pathogenesis and management of these patients.
Assuntos
DNA Mitocondrial/genética , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Mitocôndrias/genética , Mutação Puntual , Idade de Início , Surdez/genética , Diabetes Mellitus/genética , Predisposição Genética para Doença , Testes Genéticos , Variação Genética , Impressão Genômica , Humanos , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/terapia , Linhagem , Fenótipo , Doenças Retinianas/genéticaAssuntos
Distocia/tratamento farmacológico , Parassimpatolíticos/uso terapêutico , Floroglucinol/análogos & derivados , Floroglucinol/uso terapêutico , Incompetência do Colo do Útero/tratamento farmacológico , Contração Uterina/efeitos dos fármacos , Combinação de Medicamentos , Avaliação de Medicamentos , Feminino , Feto/efeitos dos fármacos , Humanos , Infusões Parenterais , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/efeitos adversos , Floroglucinol/administração & dosagem , Floroglucinol/efeitos adversos , GravidezRESUMO
CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.