A Case of Neonatal Diabetes Mellitus Due to INS Gene Mutation with Maternal Mosaicism and Atypical Presentation

Abstract

Neonatal diabetes mellitus is a single gene defect that results in diabetes mellitus in the first 6 months of life. We report a child who was diagnosed to be hyperglycemic at 13 months of life and assumed to have type 1 diabetes mellitus and started on insulin. The child came to us at 2 and 1/2 years of age. He had exceptionally good blood glucose control. His history revealed that he was symptomatic with a voracious appetite and poor weight gain since the second half of infancy. Genetic testing revealed a heterozygous mutation of the INS gene (the gene that codes for insulin). The condition has autosomal dominant inheritance. Testing the parents revealed that the mother had 7.8% mosaicism for this variant in her lymphocyte DNA. Though this did not alter the management of the patient, it did help in counseling the parents regarding risk of recurrence in future pregnancies.

Keywords

neonatal diabetes mellitus - mosaicism - INS gene

Authors' Contributions

All the authors accepted responsibility for the entire content of this submitted manuscript and approved submission.

Publikationsverlauf

Eingereicht: 21. Februar 2020

Angenommen: 26. März 2020

Artikel online veröffentlicht:
12. Mai 2020

• References

• 1 Mayer-Davis EJ, Kahkoska AR, Jefferies C. et al. ISPAD Clinical Practice Consensus Guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2018; 19 (suppl 27): 7-19
• 2 Hattersley AT, Greeley SAW, Polak M. et al. ISPAD Clinical Practice Consensus Guidelines 2018: the diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2018; 19 (July, suppl 27): 47-63
• 3 Støy J, Edghill EL, Flanagan SE. et al; Neonatal Diabetes International Collaborative Group. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A 2007; 104 (38) 15040-15044
• 4 Jain V, Satapathy A, Yadav J. et al. Clinical and molecular characterization of children with neonatal diabetes mellitus at a tertiary care center in northern India. Indian Pediatr 2017; 54 (06) 467-471
• 5 Ganesh R, Suresh N, Vasanthi T, Ravikumar KG. Neonatal diabetes: a case series. Indian Pediatr 2017; 54 (01) 33-36
• 6 Johnson SR, McGown I, Oppermann U, Conwell LS, Harris M, Duncan EL. A novel INS mutation in a family with maturity-onset diabetes of the young: variable insulin secretion and putative mechanisms. Pediatr Diabetes 2018; 19 (05) 905-909
• 7 Bee YM, Zhao Y, Ellard S, Hattersley AT, Yap F. Permanent neonatal diabetes in siblings with novel C109Y INS mutation transmitted by an unaffected parent with somatic mosaicism. Pediatr Diabetes 2014; 15 (04) 324-328
• 8 Yau D, De Franco E, Flanagan SE, Ellard S, Blumenkrantz M, Mitchell JJ. Case report: maternal mosaicism resulting in inheritance of a novel GATA6 mutation causing pancreatic agenesis and neonatal diabetes mellitus. Diagn Pathol 2017; 12 (01) 1-7
• 9 De Franco E, Shaw-Smith C, Flanagan SE, Shepherd MH, Hattersley AT, Ellard S. International NDM Consortium. GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency. Diabetes 2013; 62 (03) 993-997