Endocrine Abstracts

FPLD is a rare monogenic cause of insulin resistance. We document responses to treatment with metformin in 2 adolescent sisters with FPLD due to heterozygosity for R482W LMNA gene mutation.

The probands, aged 14 and 16 years, presented with secondary amenorrhoea, hirsutism and progressive acanthosis nigricans. Phenotypically they showed central obesity, nuchal enlargement, and thin muscular arms. These changes occurred post-pubertally. Anthrpometric and metabolic parameters of the probands, their R482W mutation positive father and three R482W negative sisters are shown in Table 1. Proband B had impaired glucose tolerance at diagnosis.

Limb MRI of the probands showed almost complete absence of subcutaneous fat; neck MRI showed lipohypertrophy. Liver ultrasound of the probands and father showed diffuse fatty infiltrate. Both probands had cystic ovaries. A therapeutic trial with metformin in both probands showed a modest improvement in insulin resistance scores(Table 1). Proband A had regression of acanthosis nigricans, Proband B regained normal glucose tolerance. Both regained menses.

This kindred demonstrate the classical phenotype associated with FPLD, including marked insulin resistance. While FPLD may be rare, it is nonetheless vital to recognise this condition, as it is associated with significant morbidity and mortality. Furthermore, while lamin mutations are associated with different diseases this particular mutation is not well studied. We document a modest decrease in insulin resistance and regression of secondary amenorrhoea in response to metformin. Further longitudinal studies are required to fully evaluate metformin as a treatment modality for FPLD.