Wolfram syndrome: case report of two siblings with genetic analysis
Keywords:
Wolfram syndrome, Diabetes mellitus, Optic atrophy
Abstract
Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder. Also known as DIDMOAD it can have variable clinical presentation at different age. We report two siblings with WS presenting at 6 and 5 years of age respectively. They presented with type I diabetes mellitus and optic atrophy. Both were compound heterozygotes for mutation on exon 8 of WS1 gene. A high index of clinical suspicion along with genetic analysis plays a key to definite diagnosis.
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References
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19. Nakagawa T, Yuan J. Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J Cell Biol. 2000;150(4):887-894. doi: 10.1083/jcb.150.4.887.
20. Hara T, Mahadevan J, Kanekura K, Hara M, Lu S, Urano F. Calcium efflux from the endoplasmic reticulum leads to β-cell death. Endocrinol. 2014;155(3):758-768. doi: 10.1210/en.2013-1519. Epub 2013 Jan 1.
2. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995;346(8988):1458-1463. doi: 10.1016/s0140-6736(95)92473-6.
3. Medlej R, Wasson J, Baz P, Azar S, Salti I, Loiselet J, Permutt A, Halaby G. Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. J Clinic Endocrinol Metabol. 2004;89(4):1656-1661. doi: https://doi.org/10.1210/jc.2002-030015.
4. Chaussenot A, Bannwarth S, Rouzier C, Vialettes B, Mkadem SA, Chabrol B, et al. Neurologic features and genotype‐phenotype correlation in Wolfram syndrome. Annals Neurol. 2011;69(3):501-508. doi: 10.1002/ana.22160. Epub 2010 Dec 28.
5. Swift RG, Sadler DB, Swift M. Psychiatric findings in Wolfram syndrome homozygotes. The Lancet. 1990;336(8716):667-669. doi: https://doi.org/10.1016/0140-6736(90)92157-D.
6. F. Urano, Wolfram Syndrome: Diagnosis, Management, and Treatment. Curr Diab Rep. 2016;16(1):1-8. doi: 10.1007/s11892-015-0702-6.
7. Kumar S. Wolfram syndrome: important implications for pediatricians and pediatric endocrinologists. Pediatr Diabetes. 2010;11(1):28-37. doi: 10.1111/j.1399-5448.2009.00518.x. Epub 2009 Dec 14.
8. Medlej R, Wasson J, Baz P, Azar S, Salti I, Loiselet J, et al. Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. J Clin Endocrinol Metab. 2004;89(4):1656-1661. doi: 10.1210/jc.2002-030015
9. Urano F, Wolfram Syndrome: Diagnosis, Management, and Treatment. Curr Diab Rep. 2016;16(1):6. doi: 10.1007/s11892-015-0702-6.
10. de Heredia ML, Clèries R, Nunes V. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. Genet Med. 2013;15(7):497-506. doi: 10.1038/gim.2012.180. Epub 2013 Feb 21.
11. Cano A, Molines L, Valéro R, Simonin G, Paquis-Flucklinger V, Vialettes B: French Group of Wolfram Syndrome. Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes. Diabetes Care. 2007;30(9):2327-2330. doi: 10.2337/dc07-0380. Epub 2007 May 29.
12. Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E et al., A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet. 1998;20(2):143-148. doi:10.1038/2441.
13. Strom TM, Hörtnagel K, Hofmann S, Gekeler F, Scharfe C, Rabl W, et al. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum Mol Genet. 1998;7(13):2021-2028. doi: 10.1093/hmg/7.13.2021.
14. Ariyasu D, Yoshida H, Hasegawa Y. Endoplasmic reticulum (ER) stress and endocrine disorders. Int J Mol Sci. 2017;18(2):382. doi: 10.3390/ijms18020382.
15. Støy J, Edghill EL, Flanagan SE, Ye H, Paz VP, Pluzhnikov A, Below JE, Hayes MG, Cox NJ, Lipkind GM, Lipton RB. Insulin gene mutations as a cause of permanent neonatal diabetes. Proceed National Acad Sci. 2007;104(38):15040-15044. doi: https://doi.org/10.1073/pnas.0707291104.
16. Cagalinec M, Liiv M, Hodurova Z, Hickey MA, Vaarmann A, Mandel M, et al. Role of mitochondrial dynamics in neuronal development: mechanism for wolfram syndrome. PLoS Biol. 2016;14(7):e1002511. doi: https://doi.org/10.1371/journal.pbio.1002511.
17. Tan Y, Dourdin N, Wu C, De Veyra T, Elce JS, Greer PA. Ubiquitous calpains promote caspase-12 and JNK activation during endoplasmic reticulum stress-induced apoptosis. J Biol Chem. 2006;281(23):16016-16024.
18. Huang CJ, Gurlo T, Haataja L, Costes S, Daval M, Ryazantsev S, Wu X, Butler AE, Butler PC. Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes. J Biol Chem. 2010;285(1):339-348. doi: 10.1074/jbc.M109.024190.
19. Nakagawa T, Yuan J. Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J Cell Biol. 2000;150(4):887-894. doi: 10.1083/jcb.150.4.887.
20. Hara T, Mahadevan J, Kanekura K, Hara M, Lu S, Urano F. Calcium efflux from the endoplasmic reticulum leads to β-cell death. Endocrinol. 2014;155(3):758-768. doi: 10.1210/en.2013-1519. Epub 2013 Jan 1.
CITATION
DOI: 10.17511/ijpr.2019.i11.06
Published: 2019-11-30
How to Cite
Singh Kochar, I., Jain, R., & Ramachandran, S. (2019). Wolfram syndrome: case report of two siblings with genetic analysis. Pediatric Review: International Journal of Pediatric Research, 6(11), 582-584. https://doi.org/10.17511/ijpr.2019.i11.06
Section
Case Report
Copyright (c) 2019 Author (s). Published by Siddharth Health Research and Social Welfare Society
This work is licensed under a Creative Commons Attribution 4.0 International License.
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