Session: SAT 758-785-Diabetes Case Reports: Type 1, Type 2, MODY & Complications
Poster Board SAT-780
Two women, referred for lipodystrophy, were studied. Cultured skin fibroblasts were used for western blot analysis, immunofluorescence microscopy, oxidative stress and senescence studies.
Two women aged 32 and 36 presented with subcutaneous peripheral lipoatrophy, truncal fat accumulation, hypertriglyceridemia, and liver steatosis. Major insulin resistance was evidenced by dramatic hyperinsulinemia following OGTT, with diabetes in one patient. Both patients had early bilateral cataracts, greying hair, distal skin atrophy and infertility, which was related to diminished follicular ovarian reserve and insulin resistance-linked ovarian hyperandrogenism. We observed biallelic WRN null mutations in both women (p.Q748X and p.Q1257X/p.M1329fs). The two patients became pregnant after metformin treatment. Pregnancies were complicated by severe cervical incompetence, leading to the preterm birth of a healthy newborn in one case, but to a second trimester abortion in the other. WRN-mutated cultured fibroblasts showed premature senescence, oxidative stress, nuclear dysmorphies and lamin abnormalities.
We show here for the first time that partial lipodystrophy with severe insulin resistance can reveal WRN-linked premature aging syndrome. Primary alterations in DNA replication and/or repair should be considered as possible causes of lipodystrophic syndromes. Cellular lamin alterations could be secondary to premature senescence and/or oxidative stress.
Nothing to Disclose: BD, PD, MA, NU, MS, RG, SO, GC, PB, PL, BC, YJB, SC, CV
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