Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is sensitive to thiazolidinediones but not to metformin
Abstract
CONTEXT: Despite the very high prevalence of the polycystic ovary syndrome (PCOS), the underlying pathogenetic mechanism has remained obscure.
OBJECTIVE: To determine the cause of two sisters' PCOS associated with severe insulin resistance.
DESIGN: Clinical case report. Methods Two sisters who presented with hyperandrogenism and menstrual disorders in the context of PCOS, and were subsequently found to be severely insulin resistant. Physical examination revealed muscular hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, in spite of excess fat deposits in the face, neck and dorsocervical region. Known genes involved in familial partial lipodystrophy were screened. At the same time, metformin (1700 mg/day) was commenced. After 2-3 years of uninterrupted therapy, lack of clinical improvement led to the introduction of pioglitazone (30 mg/day).
RESULTS: Both sisters were found to be heterozygous for the R482Q mutation in the lamin A/C gene (LMNA) gene, establishing the definitive diagnosis as Dunnigan-type familial partial lipodystrophy complicated by severe insulin resistance and secondary PCOS. Treatment with pioglitazone resulted in progressive amelioration of insulin resistance, hyperinsulinaemia and hyperandrogenaemia. Menses also improved, with restoration of a eumenorrhoeic pattern, and the framework of ultrasound PCO was in complete remission.
CONCLUSIONS: Assessment of insulin sensitivity and adipose tissue topography should be a key part…
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Evidence Hub reads this as a case report, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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