Acute Recurrent Pancreatitis in a Child With INS-Related Monogenic Diabetes and a Heterozygous Pathogenic CFTR Mutation
Open Access
- 12 December 2022
- journal article
- research article
- Published by The Endocrine Society in Journal of the Endocrine Society
- Vol. 7 (3), bvac182
- https://doi.org/10.1210/jendso/bvac182
Abstract
Given the close anatomical and physiological links between the exocrine and endocrine pancreas, diseases of one compartment often affect the other through mechanisms that remain poorly understood. Pancreatitis has been associated with both type 1 and type 2 diabetes, but its association with monogenic diabetes is unknown. Patients heterozygous for pathogenic CFTR variants are cystic fibrosis carriers and have been reported to have an increased risk of acute pancreatitis. We describe a 12-year old patient with monogenic neonatal diabetes due to a pathogenic heterozygous paternally-inherited mutation of the insulin gene (INS), c.94 G > A (p.Gly32Ser), who experienced 3 recurrent episodes of acute pancreatitis over 7 months in conjunction with poor glycemic control, despite extensive efforts to improve glycemic control in the past 4 years. Intriguingly, the maternal side of the family has an extensive history of adult-onset pancreatitis consistent with autosomal dominant inheritance and the proband is heterozygous for a maternally-inherited, CFTR variant c.3909C > G (p.Asn1303Lys). Paternally-inherited monogenic neonatal diabetes may have promoted earlier age-of-onset of pancreatitis in this pediatric patient compared to maternal relatives with adult-onset acute pancreatitis. Further study is needed to clarify how separate pathophysiologies associated with INS and CFTR mutations influence interactions between the endocrine and exocrine pancreas.Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health (P30DK020595, R01DK104942, U01DK127786)
- National Center for Advancing Translational Sciences
- National Institutes of Health (UL1TR000430)
- National Cancer Institute
- National Institutes of Health (R01CA219815)
- National Eye Institute
- National Institutes of Health (R01EY027810)
- Kovler Family Foundation
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