Lipodystrophy familial type barrosoE88.1

Barroso et al (1999)

Autosomal dominant inherited disease belonging to the family of rare familial partial lipodystrophy syndromes. Several mutations in the PPARG gene, which is located on chromosome 3p25.2 and codes for the PPARG protein (Peroxisome Proliferative Activated Receptor, gamma), which plays an essential role in the maturation of adipocytes (Miehle K et al. 2016), have been identified.

Barroso et al. reported in 1999 on a 56-year-old woman with infertility, irregular menstrual periods, insulin-dependent type II diabetes and therapy-resistant hypertension. 3 years later, clinical signs of partial lipodystrophy appeared with loss of subcutaneous fatty tissue of the extremities and the gluteal region. Furthermore, liver cirrhosis and hyperuricemia were proven.

Hegele et al (2002) reported a Canadian family (3 generations) in which 4 members showed signs of autosomal dominant familial partial lipodystrophy. A 46-year-old female family member showed a strikingly pronounced musculature of her calves and forearms, a pronounced atrophy of gluteal fat and a distinct centripetal fat distribution pattern with emphasis on the facial, neck, suprascapular and abdominal regions. The patient had been diagnosed with type II diabetes, hyperinsulinemia and type IV hyperlipoproteinemia since the age of 38. She also had irregular menstrual bleeding and bilateral polycystic ovaries. The same abnormal fat distribution was present in the other 3 affected family members. Clinically, none of the subjects showed hepatosplenomegaly, acanthosis nigricans or hirsutism.

There was evidence of missense mutations in the LMNA gene.

Agarwal and Garg (2002) reported on a 64-year-old woman who developed insulin-dependent diabetes mellitus, hypertriglyceridemia and hypertension at the age of 32 years, and about 20 years later fatty tissue loss in the extremities and face. A heterozygous mutation in the PPARG gene was detected.

The PPARG gene is located on chromosome 3p25.2 and codes for the PPARG protein (Peroxisome Proliferative Activated Receptor, gamma). Mutations and polymorphisms of the PPAR gamma protein are known to be associated with various other diseases besides partial familial lipodystrophy type 3:

• Carotide intimal medial thickness 1 OMIM: 609338
• Insulin resistance, severe, digenic OMIM: 604367
• Obesity, severe OMIM 601665

1. Agarwal A K et al (2002) A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocr Metab 87: 408-411
2. Barroso I et al (1999) Dominant negative mutations in human PPAR-gamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402: 880-883
3. Castell AL et al (2013) Vascular placental abnormalities and newborn death in a pregnant diabetic woman with familial partial lipodystrophy type 3: a possible role for peroxisome proliferator-activated receptor γ. Diabetes Metab 38:367-369.
4. Greene ME et al (1995) Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene expression 4: 281-299.
5. Hegele R A et al (2002) PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes 51: 3586-3590
6. Miehle K et al (2016) Novel peroxisome proliferator-activated receptor gamma mutation in a family with familial partial lipodystrophy type 3 Clin Endocrinol (Oxf) 84:141-148.