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- Title
A Patient with Familial Partial Lipodystrophy with a PPAR-γ Mutation and the Long-Term Effect of Leptin Therapy.
- Authors
Park, Jean Y.; Cochran, Elaine K.; Poitou, Christine; Clement, Karine; Magre, Jocelyne; Gorden, Phillip
- Abstract
Familial partial lipodystrophy (FPLD) is characterized by a loss of subcutaneous fat from the extremities and sparing of central adiposity with associated metabolic abnormalities including insulin resistance, diabetes, and hyperlipidemia. FPLD comprises a group of genetic disorders resulting from mutations of LMNA (FPLD-LMNA), encoding the nuclear lamin A/C, and less commonly, in PPARG (FPLD-PPARG), encoding the peroxisome proliferator activated receptor-γ. We report the clinical course of a patient found to have a heterozygous mutation, Arg425Cys, in PPARG. Previous studies have demonstrated the effectiveness of recombinant leptin therapy for generalized lipodystrophy and FPLD-LMNA. This represents the first report of the response of a FPLD-PPARG patient to long-term leptin therapy. A 36-year-old female born to nonconsanguinous parents developed loss of subcutaneous fat in the extremities with sparing of the face, neck, and trunk at age 13 years. At age 15 years she had severe hypertriglyceridemia, acanthosis nigricans, polycystic ovaries, hepatomegaly, hyperglycemia, and hyperinsulinemia. She had repeated episodes of pancreatitis, and eruptive xanthomas were noted with severe hypertriglyceridemia (3560 mg/dL). She was diagnosed thereafter with diabetes (HbA1c10%). In spite of maximal doses of a fibrate and several anti-diabetic medications, there was no significant improvement. She developed severe proliferative diabetic retinopathy. She was found to be hypoleptinemic (serum leptin level 2.8 ng/mL) with a body mass index of 21.9 and her body fat was 15.3%. While on 18 months of subcutaneous leptin titrated to 0.12 mg/kg/day, her acanthosis nigricans improved and HbA1c decreased from 9.9 to 7.2%. Triglycerides decreased from 1377 to 388 mg/dL, and total cholesterol decreased from 321 to 241 mg/dL. In conclusion, recombinant leptin is a unique therapy for essentially all the generalized and partial forms of lipodystrophy.
- Subjects
LIPID metabolism disorders; FAMILIAL diseases; PEROXISOMES; GENETIC mutation; LEPTIN; DIABETES complications; THERAPEUTICS
- Publication
Diabetes, 2007, Vol 56, pA581
- ISSN
0012-1797
- Publication type
Article