Unusual Association of Pancreatic Islet Cell Hyperplasia and CYP1B1 Homozygous Gene Variant in a 12-Year-Old Child
Abstract
Background: The CYP1B1 gene is typically associated with congenital glaucoma and certain cancers, but its role in metabolic regulation remains less understood. We report a case that suggests a possible new connection between CYP1B1 mutations and pancreatic islet cell hyperplasia.
Case Presentation: Our patient, a 12-year-old boy with a known history of congenital glaucoma and familial Mediterranean fever (FMF), presented with recurrent hypoglycemic episodes initially thought to be seizures due to epilepsy. Further workup revealed high insulin levels during these episodes. A PET/CT scan eventually identified a lesion in the pancreas, and surgery confirmed islet cell hyperplasia. Following resection, his hypoglycemic episodes resolved. Genetic testing revealed a homozygous mutation in CYP1B1, along with a known MEFV variant linked to FMF.
Discussion: This appears to be the first reported case linking a CYP1B1 mutation to islet cell hyperplasia. One theory is that the gene’s role in hormone and lipid metabolism, as well as oxidative stress regulation, may influence β-cell activity. Chronic inflammation from FMF could have also contributed to pancreatic stress or compensatory hyperplasia.
Conclusion: This unusual case raises important questions about the metabolic roles of CYP1B1. It also highlights the value of genetic testing in unexplained cases of hyperinsulinemic hypoglycemia, especially in patients with complex medical histories.
References
- Alsubait A, Aldossary W, Rashid M, Algamdi A, Alrfaei BM. CYP1B1 gene: Implications in glaucoma and cancer. Journal of Cancer. 2020;11(16):4652–61. Doi:10.7150/jca.42669.
- Dąbrowski A, Nowicki M, Budzyńska A, Suchodolski J, Ogórek R, Chabowski M, et al. Analysis of CYP1B1 Polymorphisms in Lung Cancer Patients Using Novel, Quick and Easy Methods Based on CAPS and ACRS-PCR Techniques. Int J Mol Sci. 2024;25(12):6676. Doi: 10.3390/ijms25126676.
- Li F, Zhu W, Gonzalez FJ. Potential role of CYP1B1 in the development and treatment of metabolic diseases. Pharmacol Ther. 2017;178:18–30. Doi: 10.1016/j.pharmthera.2017.03.007.
- Thompson, Michael J. Mordes, John P. (2015). Hypoglycemia in Pancreatic Disease.Pancreapedia: Exocrine Pancreas Knowledge Base, Doi: 10.3998/panc.2015.11.
- Palladino AA, Stanley CA. Nesidioblastosis No Longer! It’s All about Genetics. J Clin Endocrinol Metab. 2011;96(3):617–9. Doi: 10.1210/jc.2011-0164.
- Gajjar K, Martin-Hirsch PL, Martin FL. CYP1B1 and hormone-induced cancer. Cancer Letters. 2012 Nov 1-321(1):1-9. doi: 10.1016/j.canlet.2012.04.021. Epub 2012 May 2. Doi: 10.1016/j.canlet.2012.02.001
- Liehr JG. Is estradiol a genotoxic mutagenic carcinogen? Endocr Rev. 2000;21(1):40–54. Doi: 10.1210/edrv.21.1.0386.
- Tang Y, Scheef EA, Wang S, Sorenson CM, Marcus CB, Jefcoate CR, Sheibani N. “CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin 2 expression.” Blood. 2009;113(3):744–754. Doi: 10.1182/blood-2008-03-145219.
- Donath MY, Størling J, Maedler K, Mandrup-Poulsen T. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med. 2003;81(8):455–70. Doi: 10.1007/s00109-003-0450-y.
- Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol. 2009;5(4):219–26. Doi: 10.1038/nrendo.2009.21
