Background: Neonatal diabetes, diabetes diagnosed before 6 months of age, is rare, with incidence of approximately 1:90,000160,000 live births. In approximately half of cases, neonatal diabetes is transient and usually resolves between 6 and 18 months of life. In the remainder of cases, the diabetes is permanent. Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of permanent neonatal diabetes and congenital hypothyroidism with eight affected cases reported to date. We are reporting first missense mutation in GLIS3 resulting in neonatal diabetes and congenital hypothyroidism.
Case: A Libyan female, was born at full term with a weight of 2.4 kg and head circumference of 34 cm, to non-consanguineous parents. Intrauterine growth retardation was noted during pregnancy. Six weeks after birth, she was admitted to the hospital with hypovolemic shock found to have blood sugar of 1020 mg/dl without significant acidosis or ketosis. Target blood glucoses have been easy to achieve with just intermittent insulin therapy. At 5 months of age TSH found to be persistently elevated (10.7 μIU/ml) with freeT4 15.9 Pmol/l and started on levothyroxine replacement. Abdominal ultrasound scan performed at age of 6 months showed normal morphology of the liver, pancreas and both kidneys. The homozygous mutation c.1924A>T (p.Ser642Cys), was identified when the patient was tested for a monogenic etiology by sequencing a panel of 13 genes associated with neonatal diabetes. Patient now is at eight months of age with normal developmental milestones, as well as physical development and requires 0.10.2 units/kg per day of basal insulin with HbA1c 6.3%.
Conclusion: This case extends the clinical spectrum associated with mutations in GLIS3. We are describing the first case of GLIS3 gene missense mutation c.1924A>T (p.Ser642Cys) resulted in neonatal diabetes and congenital hypothyroidism. Mutations in GLIS3 should be considered in all children with neonatal diabetes without an established cause, irrespective of reported parental relatedness or insulin requirements.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology