1141-P: Characterizing Clinical Characteristics of 6q24-Related Transient Neonatal Diabetes

Abstract

Introduction: Transient neonatal diabetes mellitus (TNDM) is a heterogeneous subtype of neonatal diabetes that usually presents within the first days or weeks of life, spontaneously remits in infancy, but can recur in childhood or adolescence as a permanent form of diabetes. Approximately 70% of TNDM cases are due to overexpression of genes at chromosome 6q24 caused by one of three potential mechanisms: uniparental disomy (UPD6), paternal duplication, or hypomethylation of the maternal allele. Our aim was to further elucidate clinical characteristics of a relatively large group of individuals with this rare condition. Methods: Participants with a confirmed or suspected diagnosis of 6q24 TNDM were identified through the University of Chicago Monogenic Diabetes Registry. Research based genetic testing was provided. Clinical information was extracted from survey responses and medical records. Results: There were thirty-three participants with 6q24-TNDM (58% male). Eight (24%) had hypomethylation of the maternal allele, seven (21%) had paternal duplication, seventeen (52%) had UPD6, and one had UPD6 vs. hypomethylation of the maternal allele. The mean age of initial diabetes presentation was 4.6 days (n=33). Remission occurred at a mean age of 4.5 months (n=28). Nine participants reported having relapse of diabetes, with a mean age of relapse of 17.4 years (range 12 - 31 years). There were six participants who reported umbilical hernia (22%, n=27), fifteen participants reported macroglossia (54%, n=27), and ten (36%, n=28) indicated speech therapy was required. No significant differences in clinical characteristics were identified across the three mechanisms (UPD6, paternal duplication, hypomethylation). Conclusions: Clinical characteristics were not different across mechanism groups, suggesting that genetic testing is required to definitively determine a mechanism and diagnosis of 6q24 TNDM. Early assessment for speech therapy should be considered for this patient population. Disclosure M.Mccullough: None. L.R.Letourneau-freiberg: None. T.L.Bowden: Stock/Shareholder; Procter & Gamble, OPKO Biologics, Ltd. B.Kandasamy: None. D.Del gaudio: None. L.H.Philipson: Advisory Panel; Nevro Corp., Research Support; Novo Nordisk, Dompé, Provention Bio, Inc., Imcyse, Novo Nordisk Foundation. S.W.Greeley: None. Funding National Institutes of Health (R01DK104942, P30DK020595)