Genetics of Lipodystrophy.

Lipodystrophy disorders are characterized by selective loss of fat tissue with metabolic complications including insulin resistance, hypertriglyceridemia, and nonalcoholic liver disease. These complications can be life-threatening, affect quality of life, and result in increased health care costs. Genetic discoveries have been particularly helpful in understanding the pathophysiology of these diseases, and have shown that mutations affect pathways involved in adipocyte differentiation and survival, lipid droplet formation, and lipid synthesis. In addition, genetic testing can identify patients whose phenotypes are not clearly apparent, but who may still be affected by severe metabolic complications.

[Familial partial lipodystrophy type 1. A rare or underdiagnosed syndrome?]. / Lipodistrofia parcial familiar tipo 1. ¿Un síndrome subdiagnosticado o raro?

Familial partial lipodystrophy (FPL) type 1 is a syndrome characterized by loss of subcutaneous fat in arms and legs and an excess of body fat in face, neck, and torso. This rare syndrome is usually diagnosed when patients present cardiovascular complications or pancreatitis due to the severe metabolic abnormalities. Here we present the case of a 45 year old diabetic female without any pathological family history, a poor glycemic control (HbA1c 11.7%), hypertriglideridemia (3000 mg/dl), a body mass index (BMI) of 38, thin limbs, subcutaneous fat loss in gluteal area and ledge of fat above them, prominent veins in lower extremities, moon face, and acanthosis nigricans; as well as hypertension (150/100 mmHg) and subcutaneous folds measuring less than average were observed. Hypercortisolism was discarded and leptin levels were measured (16.8 mg/ml, VR: BMI > 30: 50 mg/ml). Due to these clinical and biochemical manifestations, and low leptin levels (16.8 mg/ml), Kobberling syndrome was suspected; however, LMNA mutation analysis was negative. Changes in lifestyle and treatment with fenofibrate, biphasic insulin 50/50, and enalapril were initiated showing a a significant metabolic improvement: HbA1c (7.8%) and TG (243 mg/dl). FPL type 1 is a familial disease, although there are spontaneous cases. No specific mutation is responsible for this syndrome. Due to its clinical manifestations, Cushing syndrome must be discarded.

Lipodistrofia parcial familiar tipo 1: ¿Un síndrome subdiagnosticado o raro?

La lipodistrofia parcial familiar de tipo1 (LPF 1) es un síndrome caracterizado por la pérdida parcial de grasa subcutánea en extremidades con distribución incrementada de la misma en rostro, cuello y tronco. Es una identidad familiar aunque hay casos espontáneos. Hasta ahora no se conoce mutación responsable. Se debe realizar diagnóstico diferencial con el síndrome de Cushing. Es un síndrome poco frecuente y en oportunidades se llega al diagnóstico cuando los pacientes presentan complicaciones cardiovasculares o afectación pancreática como consecuencia de una grave alteración metabólica. Se presenta el caso de una paciente de 45 años con diabetes mellitus desde los 20 años de edad, mal control glucémico (HbA1c: 11.7%) e hipertrigliceridemia (TG: 3000 mg/dl), índice de masa corporal (IMC): 38, extremidades adelgazadas, pérdida de grasa subcutánea en glúteos, sobreelevación de pliegue por encima de los mismos, venas prominentes en miembros inferiores, cara de luna llena y marcada acantosis nigricans, hipertensión (TA: 150/100 mm Hg) y medidas de pliegues subcutáneos disminuidos. El dosaje de leptina fue 16.8 mg/ml. El estudio genético para gen LMNA fue negativo. Se instauraron medidas de cambio de estilo de vida, tratamiento con fenofibrato, insulina premezcla 50/50 y enalapril, obteniéndose una franca mejoría clínica, de la HbA1c (7.8%) y de los TG (243 mg/dl).

Familial partial lipodystrophy (FPL) type 1 is a syndrome characterized by loss of subcutaneous fat in arms and legs and an excess of body fat in face, neck, and torso. This rare syndrome is usually diagnosed when patients present cardiovascular complications or pancreatitis due to the severe metabolic abnormalities. Here we present the case of a 45 year old diabetic female without any pathological family history, a poor glycemic control (HbA1c 11.7%), hypertriglideridemia (3000 mg/dl), a body mass index (BMI) of 38, thin limbs, subcutaneous fat loss in gluteal area and ledge of fat above them, prominent veins in lower extremities, moon face, and acanthosis nigricans; as well as hypertension (150/100 mmHg) and subcutaneous folds measuring less than average were observed. Hypercortisolism was discarded and leptin levels were measured (16.8 mg/ml, VR: BMI > 30: 50 mg/ml). Due to these clinical and biochemical manifestations, and low leptin levels (16.8 mg/ml), Kobberling syndrome was suspected; however, LMNA mutation analysis was negative. Changes in lifestyle and treatment with fenofibrate, biphasic insulin 50/50, and enalapril were initiated showing a a significant metabolic improvement: HbA1c (7.8%) and TG (243 mg/dl). FPL type 1 is a familial disease, although there are spontaneous cases. No specific mutation is responsible for this syndrome. Due to its clinical manifestations, Cushing syndrome must be discarded.

Lipodistrofia parcial familiar tipo 1: ¿Un síndrome subdiagnosticado o raro?

La lipodistrofia parcial familiar de tipo1 (LPF 1) es un síndrome caracterizado por la pérdida parcial de grasa subcutánea en extremidades con distribución incrementada de la misma en rostro, cuello y tronco. Es una identidad familiar aunque hay casos espontáneos. Hasta ahora no se conoce mutación responsable. Se debe realizar diagnóstico diferencial con el síndrome de Cushing. Es un síndrome poco frecuente y en oportunidades se llega al diagnóstico cuando los pacientes presentan complicaciones cardiovasculares o afectación pancreática como consecuencia de una grave alteración metabólica. Se presenta el caso de una paciente de 45 años con diabetes mellitus desde los 20 años de edad, mal control glucémico (HbA1c: 11.7%) e hipertrigliceridemia (TG: 3000 mg/dl), índice de masa corporal (IMC): 38, extremidades adelgazadas, pérdida de grasa subcutánea en glúteos, sobreelevación de pliegue por encima de los mismos, venas prominentes en miembros inferiores, cara de luna llena y marcada acantosis nigricans, hipertensión (TA: 150/100 mm Hg) y medidas de pliegues subcutáneos disminuidos. El dosaje de leptina fue 16.8 mg/ml. El estudio genético para gen LMNA fue negativo. Se instauraron medidas de cambio de estilo de vida, tratamiento con fenofibrato, insulina premezcla 50/50 y enalapril, obteniéndose una franca mejoría clínica, de la HbA1c (7.8%) y de los TG (243 mg/dl).(AU)

Familial partial lipodystrophy (FPL) type 1 is a syndrome characterized by loss of subcutaneous fat in arms and legs and an excess of body fat in face, neck, and torso. This rare syndrome is usually diagnosed when patients present cardiovascular complications or pancreatitis due to the severe metabolic abnormalities. Here we present the case of a 45 year old diabetic female without any pathological family history, a poor glycemic control (HbA1c 11.7%), hypertriglideridemia (3000 mg/dl), a body mass index (BMI) of 38, thin limbs, subcutaneous fat loss in gluteal area and ledge of fat above them, prominent veins in lower extremities, moon face, and acanthosis nigricans; as well as hypertension (150/100 mmHg) and subcutaneous folds measuring less than average were observed. Hypercortisolism was discarded and leptin levels were measured (16.8 mg/ml, VR: BMI > 30: 50 mg/ml). Due to these clinical and biochemical manifestations, and low leptin levels (16.8 mg/ml), Kobberling syndrome was suspected; however, LMNA mutation analysis was negative. Changes in lifestyle and treatment with fenofibrate, biphasic insulin 50/50, and enalapril were initiated showing a a significant metabolic improvement: HbA1c (7.8%) and TG (243 mg/dl). FPL type 1 is a familial disease, although there are spontaneous cases. No specific mutation is responsible for this syndrome. Due to its clinical manifestations, Cushing syndrome must be discarded.(AU)