Shwachman-Diamond Syndrome and Type 1 Diabetes Mellitus: More Than a Chance Association?

Abstract

Shwachman-Diamond syndrome is a rare clinical condition consisting of exocrine pancreatic dysfunction, various degree of pancytopenia, and metaphyseal dysplasia. The majority of Shwachman-Diamond syndrome cases result from mutations in the Shwachman-Bodian-Diamond Syndrome gene. To date, type 1 diabetes mellitus has only been reported in 4 independent cases presenting with Shwachman-Diamond syndrome, 3 of them with molecular confirmation of the diagnosis. We describe 2 unrelated patients with clinical and molecular features typical of Shwachman-Diamond syndrome and type 1 diabetes mellitus. In addition, we report the occurrence rate of type 1 diabetes mellitus in the Italian registry for Shwachman-Diamond syndrome, which is low (3.23%) but increased at least 30-fold over the type 1 diabetes mellitus occurrence rate in the general population. No evidence of a direct correlation between Shwachman-Diamond syndrome and type 1 diabetes mellitus have been reported, therefore the presence of both diseases in the same patient might be a chance association, however we suggest that the defects in immune regulation of Shwachman-Diamond syndrome might play a role in the development of type 1 diabetes mellitus.

Key words

Shwachman-Diamond syndrome - type 1 diabetes mellitus - cell-mediated immunity

References

• 1 Aggett PJ, Cavanagh NP, Matthew DJ. et al . Shwachman's syndrome. A review of 21 cases.  Arch Dis Child. 1980;  55 331-347
• 2 Anwar AJ, Walker JD, Frier BM. Type 1 diabetes mellitus and Downs syndrome: prevalence, management and diabetic complications.  Diabetic Med. 1998;  15 160-163
• 3 Boocock GR, Morrison JA, Popovic M. et al . Mutations in SBDS are associated with Shwachman-Diamond syndrome.  Nat Genet. 2003;  33 97-101
• 4 Burroughs L, Woolfrey A, Shimamura A. Shwachman-Diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment.  Hematol Oncol Clin North Am. 2009;  23 (2): 233-248
• 5 Craig ME, Hattersley A, Donaghue KC. Definition, epidemiology and classification of diabetes in children and adolescents.  Pediatr Diabetes. 2009;  10 (S 12) 3-12
• 6 Dror Y, Ginzberg H, Dalal I. et al . Immune function in patients with Shwachman-Diamond syndrome.  Br J Haematol. 2001;  114 (3): 712-717
• 7 Elder DA, Kaiser-Rogers K, Aylsworth AS. et al . Type I Diabetes Mellitus in a Patient With Chromosome 22q11.2 Deletion Syndrome.  Am J Med Gen. 2001;  101 17-19
• 8 Filippi L, Tronchin M, Pezzati M. et al . Shwachman syndrome in a preterm newborn associated with transient diabetes mellitus.  J Pediatr Gastroenterol Nutr. 2002;  34 219-223
• 9 Fujishiro M, Ogihara T, Tsukuda K. et al . A case showing an association between type 1 diabetes mellitus and Kabuki syndrome.  Diabetes Res Clin Pract. 2003;  60 (1): 25-31
• 10 Ginzberg H, Shin J, Ellis L. et al . Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar.  J Pediatr. 1999;  135 81-88
• 11 Kamoda T, Saito T, Kinugasa H. et al . A case of Shwachman-Diamond syndrome presenting with diabetes from early infancy.  Diabetes Care. 2005;  28 (6): 1508-1509
• 12 Kawashima H, Ushio M, Aritaki K. et al . Discordant endocrinopathy in a sibling with Shwachman-Diamond syndrome.  J Trop Pediatr. 2006;  52 (6): 445-447
• 13 Knip M, Siljander H. Autoimmune mechanisms in type 1 diabetes.  Autoimmunity Reviews. 2008;  7 550-557
• 14 Kurtoglu S, Atabek ME, Kumandas S. et al . Diabetes mellitus type 1: association with Rett syndrome.  Pediatr Int. 2005;  47 (1): 90-91
• 15 Mack DR, Forstner GG, Wilschanski M. et al . Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression.  Gastroenterology. 1996;  111 1593-1602
• 16 Mortensen KH, Cleemann L, Hjerrild BE. et al . Increased prevalence of autoimmunity in Turner syndrome-influence of age.  Clin Exp Immunol. 2009;  156 (2): 205-210
• 17 Pamuk BO, Torun AN, Kulaksizoglu M. et al . 49,XXXXY syndrome with autoimmune diabetes and ocular manifestations.  Med Princ Pract. 2009;  18 (6): 482-485
• 18 R Development Core Team. . R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.  ISBN 3-900051-07-0, URL http://www.R-project.org 2010; 
• 19 Rommens JM, Durie PR. Shwachman-Diamond syndrome. In: GeneReviews. (Accessed May 24, 2010 at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sds. )
• 20 Rosendahl J, Teich N, Mossner J. et al . Compound heterozygous mutations of the SBDS gene in a patient with Shwachman-Diamond syndrome, type 1 diabetes mellitus and osteoporosis.  Pancreatology. 2006;  6 (6): 549-554
• 21 Shmerling DH, Prader A, Hitzig WH. et al . The syndrome of exocrine pancreatic insufficiency, neutropenia, metaphyseal dysostosis and dwarfism.  Helv Paediatr Acta. 1969;  24 547-575
• 22 Vespasiani G, Nicolucci A, Giorda C. Epidemiologia del diabete. In: Annali della Sanità Pubblica, 2005

Correspondence