Dunnigan-type familial partial lipodystrophy associated with the heterozygous R482W mutation in LMNA gene - case study of three women from one family.

Lipodystrophies are a heterogeneous group of diseases affecting adipose tissue distribution. Familial partial lipodystrophy of the Dunnigantype (FPLD) is a rare autosomal, dominant disorder caused by missense mutations in lamin A/C (LMNA) gene where selective loss of subcutaneous adipose tissue from the limbs and trunk, and accumulation of fat in the neck and face, is usually associated with a variety of metabolic disorders including insulin resistance, diabetes mellitus, dyslipidemia, hepatic steatosis and high blood pressure.In this report we present clinical and molecular features of three Polish women with FLPD phenotype coming from one family (a motherand her two daughters). FPLD was recognised under the circumstances of diabetes treatment, where sequencing of LMNA gene revealed heterozygous R482W mutation. In order to be able to recognise monogenic diabetes associated with lipodystrophy, it is important to bevery precise in physical examination while diagnosing diabetes and to be aware of the necessity of performing genetic testing. Diabetes appropriate differential diagnosis is essential for the treatment strategy, anticipation of the disease progression, and determination of the prognosis. It is necessary for an individual mutation carrier to look carefully at the patient's family.

Éxito reproductivo en embarazo de madre portadora de diabetes lipoatrófica generalizada / Reproductive successful in pregnancy of mother with generalized lipoatrophic diabetes

Se presenta el caso de una paciente portadora de diabetes lipoatrófica generalizada con éxito reproductivo. Se analiza el tratamiento metabólico y el manejo perinatal. La instalación de infección intraamniótica determinó la interrupción del embarazo a las 28 semanas, con recién nacido de pretérmino adecuado para la edad gestacional, que evolucionó con distrés respiratorio prolongado, hemorragia subaracnoidea y enterocolitis necrotizante. El seguimiento al sexto mes de vida revela examen neurológico normal.

Transgenic mice lacking white fat: models for understanding human lipoatrophic diabetes.

The human disease lipoatrophic (or lipodystrophic) diabetes is a rare syndrome in which a deficiency of adipose tissue is associated with Type 2 diabetes. This disease is an interesting contrast to the usual situation in which diabetes is associated with obesity, an excess of fat. Aside from obesity, patients with lipodystrophic diabetes have the other features associated with Metabolic Syndrome X, including hypertension and dyslipidemia. The contrast between diabetes with a lack of fat and diabetes with an excess of fat provides an opportunity to study the mechanisms causing Type 2 diabetes and its complications. Recently, three laboratories have produced transgenic mice that are deficient in white adipose tissue. These mice have insulin resistance and other features of lipoatrophic diabetes, and are a faithful model for the human disease. Here we review the different murine models of fat ablation and compare the murine and human diseases, addressing the questions: Is the lack of fat causative of the diabetes, and if so by what mechanism? How could the other clinical features be explained mechanistically? And finally, what can be gleaned about insight into treatment options?

Successful pregnancy outcome in association with lipoatrophic diabetes mellitus.

Lipoatrophic diabetes mellitus is a rare syndrome characterized by lipoatrophy and insulin-resistant diabetes mellitus. Partial lipodystrophy without clinical diabetes mellitus has been associated with intrauterine growth retardation and fetal death. We report successful pregnancy outcomes in two women with lipoatrophic diabetes mellitus.

Lipoatrophic diabetes: endocrine dysfunction and the response to control hypertriglyceridemia.

Endocrine function was studied in a 24 year old female with lipoatrophic diabetes (LD). Baseline endocrine studies (serum triglycerides: 2600 mg/dl) demonstrated hyperprolactinemia (serum prolactin 51 ng/ml), increased ACTH levels, absence of suppression of ACTH to a high dose of dexamethasone which suppressed serum cortisol normally and, hyperresponsiveness of TSH to stimulation with TRH. Thyroid hormone levels (total and free fraction) were essentially normal. Major metabolites of thyroid hormone (T3, rT3, 3, 3'-T2, and 3', 5'-T2) were also normal and exhibited a normal response to the administration of L-thyroxine and propylthiouracil. Exchange of 84% of the patient's plasma resulted in a decrease in serum triglycerides (700 mg/dl) which was followed by a rebound to the original level in seven days. After the sixth plasmapheresis serum triglycerides stabilized at less than 1000 mg/dl. Plasmapheresis was associated with the appearance of amenorrhea and galactorrhea; also hypertension and proliferative retinopathy developed during this therapy. Repeat endocrine function studies (serum triglycerides: 700 mg/dl) showed a further rise in serum prolactin (greater than 160 ng/ml), persistence of abnormal ACTH secretion and normalization of TSH responsiveness. Lipoatrophic diabetes is associated with abnormal central endocrine function but appropriate peripheral target gland secretion. A course of plasmapheresis improves the hypertriglyceridemia but not the endocrine dysfunction. In this patient with LD the most important side effect of plasmapheresis was the development of cardiovascular complications.