SUN-LB033 New Onset Diabetes in a Post-Renal Transplant Pediatric Patient with a Mutation of the Hepatocyte Nuclear Factor-1β Gene

Abstract

Abstract Background: Maturity onset diabetes of the young (MODY) 5 is a rare type of dominantly inherited diabetes mellitus (DM). It is caused by mutations of the hepatocyte nuclear factor-1beta (HNF-1 beta) gene. Most are missense mutations that produce truncated proteins resulting in a variable clinical spectrum that may include kidney, genital and pancreatic abnormalities. We describe a case of a young patient diagnosed with DM after renal transplant; also, his diagnosis disclosed extensive family history of DM. Case: Six-year-old African-American patient with history of end stage renal disease due to bilateral cystic dysplasia presented with significant hyperglycemia three days after renal transplant. Polycystic kidney disease observed in prenatal ultrasound led to genetic testing. He was found to have a 1.0-1.8Mb deletion on chromosome microarray at 17q12 that included TCF2/HNF1B genes. His HbA1C was 5.8% at time of endocrine evaluation. He received one time high dose steroids in operating room and was started on tacrolimus after transplant. Pancreatic ultrasound showed normal pancreatic head, body not visualized. He was sent home with intensive insulin management on day 20 after renal transplant. Patient’s family history revealed mother with diagnosis of type 2 diabetes mellitus (T2DM) at age 19, maternal grandmother and great-grandmother diagnosed at early age with T2DM as well. Discussion: HNF-1 beta gene encodes a transcription factor that regulates nephron and embryonic pancreas development. MODY 5 is clinically heterogeneous disorder and the degree of insulin deficiency is variable, some family members who carry the gene remain free of diabetes into later adult life. The mean age of diagnosis of DM is 26 years with a range of 10–61 years. Our patient is only six years old and he may have presented earlier due post-transplant status, high dose steroids and tacrolimus use, all factors known to be triggers for hyperglycemia but the persistence of insulin requirement and levels of HbA1C being on pre-diabetes range at time of evaluation might be a sign of early deterioration of pancreatic function. Diagnosis of MODY5 has important implications for treatment, prognosis, and genetic counseling. Diabetes in these patients requires early use of insulin. Patient’s family members were advised to undergo genetic testing and screening for renal abnormalities and DM. Further studies on the correlation of phenotypes and genotypes will help delineate the clinical course of MODY 5. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.