ESPE Abstracts

Introduction: The main type of diabetes seen in pediatric clinical practice is type 1 diabetes. Monogenic diabetes and syndromic diabetes are rare, but can be more common in areas where consanguinity is high.

A 12-year-old girl born to consanguineous parents who are first cousins, was referred after being diagnosed with diabetes and severe diabetic ketoacidosis. In addition, she had hypertrichosis, coarse facial features, acanthosis nigricans, a high arched palate, overcrowded teeth, short stature (height 134 cm /-2.4 SD) and a bone age of 9 years. Her tanner staging was B1P2A1. Her psychomotor development was normal.

Past medical history revealed bilateral oophorectomy at the age of 63 days. This was due to the presence of bilateral multiple ovarian cysts, diagnosed at the time as Juvenile Granulosa cell tumor.

Her initial investigations showed insulin resistant diabetes and growth hormone deficiency:

C peptide; 12.54 ng/ml (n: 1.1−4.4 ng/ml)

IGF1; 65 ng/ml (−2 SD)

She is now on total daily dose of 84 U insulin (2.6 U/kg) and her HbA1c is 10%.

At the age of 13.9 years she was 139.5 cm (−3.1 SD) and her bone age was 10 years. Growth hormone stimulation was done with glucagon, showing growth hormone deficiency. Growth velocity was 4 cm/year. She was put on growth hormone and sex steroid replacement therapy.

Whole Exome Sequencing (WES) was carried out. Detected variants were filtered using bioinformatic software (Ingenuity and Varaft). She was found to be homozygous for a known pathogenic variant p.Thr937Met (c.2810C>T) in the INSRgene causing Rabson–Mendenhall syndrome her parents tested heterozygous for the same variant.

Conclusion: The incidence of Rabson–Mendenhall syndrome is estimated to be less than 1 in a million people. Insulin resistant diabetes mellitus, short stature, dysmorphic features, multiple ovarian cysts and hypogonadotropic hypogonadism have been described in these patients. In our case, the patient has hypergonadotropic hypogonadism due to a bilateral oophorectomy which may not have been indicated. Genetic testing in such cases of complicated diabetes with other phenotypic features could facilitate appropriate diagnosis and treatment.

The study relating to this case is funded by AZV grant number NV18-01-00078.