Peroxisome proliferator-activated receptor gamma mutation in familial partial lipodystrophy type three: A case report and review of literature

World J Diabetes. 2024 Dec 15;15(12):2360-2369. doi: 10.4239/wjd.v15.i12.2360.

Abstract

Background: Familial partial lipodystrophy disease (FPLD) is a collection of rare genetic diseases featuring partial loss of adipose tissue. However, metabolic difficulties, such as severe insulin resistance, diabetes, hypertriglyceridemia, and hypertension frequently occur alongside adipose tissue loss, making it susceptible to misdiagnosis and delaying effective treatment. Numerous genes are implicated in the occurrence of FPLD, and genetic testing has been for conditions linked to single gene mutation related to FPLD. Reviewing recent reports, treatment of the disease is limited to preventing and improving complications in patients.

Case summary: In 2017, a 31-year-old woman with diabetes, hypertension and hypertriglyceridemia was hospitalized. We identified a mutation in her peroxisome proliferator-activated receptor gamma (PPARG) gene, Y151C (p.Tyr151Cys), which results in a nucleotide substitution residue 452 in the DNA-binding domain (DBD) of PPARG. The unaffected family member did not carry this mutation. Pioglitazone, a PPARG agonist, improved the patient's responsiveness to hypoglycemic and antihypertensive therapy. After one year of treatment in our hospital, the fasting blood glucose and glycosylated hemoglobin of the patient were close to normal.

Conclusion: We report a rare PPARG mutation, Y151C, which is located in the DBD of PPARG and leads to FPLD, and the preferred agent is PPARG agonists. We then summarized clinical phenotypic characteristics of FPLD3 caused by PPARG gene mutations, and clarified the relationship between different mutations of PPARG gene and the clinical manifestations of this type of FPLD. Additionally, current treatments for FPLD caused by PPARG mutations are reviewed.

Keywords: Case report; Familial partial lipodystrophy; Peroxisome proliferator-activated receptor gamma; Phenotypic heterogeneity; Tyr151Cys.

Publication types

  • Case Reports