Familial partial lipodystrophy (FPLD) syndromes are rare heterogeneous disorders especially in women characterized by selective loss of adipose tissue, reduced
leptin levels and severe metabolic abnormalities. Here we report a 34-year-old female with a novel heterozygotic c.485
thymine>
guanine (T>G) missense variant (p.phenylalanine162cysteine; (Phe162Cys)) in exon 4 of the
peroxisome proliferator-activated receptor gamma (PPARG) gene, developing a non-ketotic diabetes and severe
hypertriglyceridemia with
triglyceride concentrations >50 mmol/L. In this case, a particular interesting feature in comparison to other known PPARG mutations in FPLD is that while glycaemic control could be achieved through standard anti-diabetic medication,
hypertriglyceridemia did neither respond to
fibrate nor to omega-3-fatty
acid therapy. This might suggest a lipid metabolism driven phenotype of the novel PPARG c.485T>G missense variant. Notably, recombinant
leptin replacement
therapy (
metreleptin (Myalepta®)) was initiated showing a rapid and profound effect on
triglyceride levels as well as on liver function tests and satiety feeling. Unfortunately, severe allergic skin reactions developed at the side of injection which could be covered by anti-histaminc treatment. We conclude that the heterozygous PPARG c.485T>G variant is a yet undescribed molecular basis underlying FPLD with difficulties predominantly to control
hypertriglyceridemia and that recombinant
leptin therapy may be effective in affected subjects.
LEARNING POINTS: Heterozygous c.485T>G variant in PPARG is most likely a cause for FPLD in humans. This variant results in a special metabolic phenotype with a predominant dysregulation of
triglyceride metabolism not responding to standard
lipid lowering
therapy. Recombinant
leptin therapy is effective in rapidly improving
hypertriglyceridemia.