ESPE Abstracts

Background: The transcription factor Gli-similar 3 (Glis3) is predominantly expressed in the pancreas and it has a critical role in the development of insulin producing β-cells, thyroid and kidney. Mutations in GLIS3 is a rare cause of neonatal diabetes associated with congenital hypothyroidism, congenital glaucoma and polycystic kidney. We report a new case from consanguineous parents with homozygous novel mutation in GLIS3 gene.

Case presentation: our patient is a male child, who was born with a weight of 1900g, length of 44 cm and head circumference of 44 cm after 39 weeks of gestation. He was hospitalized at the age of 15 days for weight loss without digestive disorder or dietary error. His weight was1800g (below the third percentile). The biological analysis revealed hyperglycemia (blood glucose: 35 mmol/l) associated with glucosuria without ketonuria requiring continuous intravenous insulin (0.05 IU/kg/h) and was subsequently treated with subcutaneous insulin (Actrapid^® then a mixture of Actrapid^® and Insulatard^®, two injection regimen). He had a high level of insulinemia (44.8 mU /l) and a low level of C peptide (0.43 µg/l). Ultrasonography and CT scan revealed normal appearance of the pancreas. At the 25^th day of life, he developed macroglossia and edema. Thyroid assessment showed free thyroxine (FT4) of 1.2 pmol/l (normal: 12–22) and serum TSH of 46 µIU/l (normal: 0.27–4.5), which required a treatment with L-thyroxine (10mcg/kg/d). Anti-thyroglobulin and anti-microsome antibodies were negative. Thyroid ultrasound showed normal thyroid lobes, and the scintigraphy did not shown any fixation. After 5 months of follow-up, he developed dysmorphic syndrome (bulging forehead, micrognathism and badly hemmed ears), convergent strabismus, glaucoma, bilateral perception deafness, epilepsy with psychomotor retardation. Liver assessment did not shown cholestasis and renal echograhy did not shown renal cysts. Target blood glucose have been difficult to achieve due to labile glucose level. Glycosylated haemoglobin was between 8 and 12%. Genetic assessment revealed homozygous stop mutation GLIS3: C1597c A / p S 295x with new phenotype.

Conclusion: this case is characterized by the absence of renal and hepatic involvement and a particular clinical phenotype with psychomotor retardation and epilepsy.