ESPE Abstracts

We present the case of a now 11 years old girl with the ultra-rare severe insulin resistance Rabson-Mendenhall syndrome due to the previously undescribed compound heterozygous mutations exon 16: c.2986A>G (Paternal) and intron 9: c.2029+1G>T (maternal) of the insulin receptor gene. The phenotypic findings were composed of dystrophy (birth weight 1970g, small for gestational age), hyperglycemia (up to 400mg/dl), severe acanthosis nigricans and mild cardiac septal hyperplasia. Insulin resistance was pronounced (insulin level 2074mU/I), with development of diabetes mellitus. At 7 months of age, conspicuous tooth formation was evident. On ultrasound, polycystic ovaries could be detected at the age of 18 months. Furthermore, with increasing age, the presence of generalized lipodystrophy was evident. Due to severe short stature and IGF-I deficiency (IGF-I -8,1SDS, IGFBP3 -9,42 SDS) treatment with recombinant IGF-I (0.12mg/kgBW/d) was initiated at the age of 2 years with a height SDS of -4.39 SDS. Satisfactory catch-up growth (height SDS -1.92 at the age of 9 years) and stable long-term blood glucose levels (HbA1C ≤6.2% until the age of 7 years) could be obtained. However, metabolic control worsened (HbA1C 8.3% and LDL-cholesterol 252 mg/dl at the age of 10 years). Therefore, an additional treatment with metreleptin s.c. was started (0.08mg/kgBW/d) BMI was -1,37 SDS. After 9 months, metabolic control improved (HbA1C 7.4%, LDL-cholesterol 167 mg/dl), but BMI further decreased to -1.98 despite good appetite.

Conclusion: To our knowledge, this is the first report of combined treatment with rhIGF-I and metreleptin in severe insulin resistance syndrome showing short-term improvement in metabolic control.