ESPE Abstracts (2016) 86 P-P2-581

Missense Mutation of GLIS3 Gene Resulting Inneonatal Diabetes and Congenital Hypothyroidism

Nadia Alghazira, Omalmir Gedafi Fathallaa, Ibtisam Hadeeda, Milad Algouila, Milad Abusagb, Milad Doggahaa, Hamida Alsahlic, Suliman Abusrewila & Louis Philipson Philipsonb

aTripoli Medical Center, Tripoli, Libya, North Africa, Libya; bDepartment of Medicine, Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, IL USA; cKhadra Hospital, Tripoli, Libya, North Africa, Libya

Background: Neonatal diabetes, diabetes diagnosed before six months of age, is rare, with incidence of approximately 1:90 000–160 000 live births. In approximately half of cases, neonatal diabetes istransient 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.

Objective and hypotheses: To evaluate and present non classical situation for a case of neonatal diabetes and. As well as sequence correlation between neonatal diabetes and hypothyroidism in missens mutation in genetic studies.

Method: One infant Libyan female 6 weeks old, she was presented with hypovolemic shock in ketotic state and markedly raised her blood sugar 1020 mg/dl. the patient was managed according her condition and discharged on basal insulin. Consequently at 5 month of her age developed hypothyroidism. Evaluations the patient clinically and genetic studies was done were found first missens mutation resulting in her condition.

Results: 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 easyto achieve with just intermittent insulin therapy. At five months of age TSH found to be persistently elevated (10.7 μIU/ml) with free T4 15.9 Pmol/l and started on levothyroxine replacement. Abdominal ultrasound scan performed at age of six 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 0.1–0.2 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 describingthe 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.