Alternative titles; symbols
SNOMEDCT: 724540009; ORPHA: 103918;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q32 | {Fibrocalculous pancreatic diabetes, susceptibility to} | 608189 | Autosomal dominant; Autosomal recessive | 3 | SPINK1 | 167790 |
| 5q32 | Tropical calcific pancreatitis | 608189 | Autosomal dominant; Autosomal recessive | 3 | SPINK1 | 167790 |
A number sign (#) is used with this entry because tropical calcific pancreatitis (TCP) is caused by mutation in the pancreatic secretory trypsin inhibitor gene (SPINK1; 167790). Evidence suggests that in some patients, mutated SPINK1 cannot cause disease independently by autosomal dominant or recessive mechanisms and that the presence of a second mutation, either in the same gene or other genes, is required for expression of the disease phenotype.
Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to tropical regions. Large intraductal calculi are present, and evidence of pancreatic calcification is seen on imaging studies (summary by Mahurkar et al., 2006).
TCP is an idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to TCP (Mohan et al., 1989). TCP differs from alcoholic pancreatitis by a younger age at onset, pancreatic calcification, a high incidence of insulin-dependent but ketosis-resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer (Chandak et al., 2002).
In 68 patients from India with clinically and radiologically confirmed TCP (24 with FCPD and 44 with TCP without diabetes mellitus), Chandak et al. (2002) analyzed for mutations in the PRSS1 and SPINK1 genes. No mutation was detected in the PRSS1 gene in these patients. They identified compound heterozygosity for an asn34-to-ser mutation in the SPINK1 gene (N34S; 167790.0001) and a -215G-T promoter mutation that was not found in any of 100 controls. All 3 patients had late-onset disease with diabetes mellitus, consistent with the fibrocalculous pancreatic diabetes phenotype. Of the other patients with TCP, 8 were homozygous for N34S, 22 were heterozygous for N34S, and 1 was heterozygous for N34S and another mutation in the SPINK1 gene. Analysis of the phenotype in terms of the age at onset, frequency of attacks, and presence and age at onset of diabetes mellitus did not show any significant difference between N34S heterozygous or homozygous patients. Because the N34S heterozygous and homozygous patients had a similar phenotype, Chandak et al. (2002) presumed that mutated SPINK1 cannot cause disease independently by autosomal dominant or recessive mechanisms and that the presence of a second mutation, either in the same gene or other genes, is required for expression of the disease phenotype.
Mahurkar et al. (2006) found an association between the val26 allele of a leu26-to-val polymorphism (rs12338) in the CTSB gene (116810) in patients with tropical calcific pancreatitis; the association appeared to be independent of SPINK1 mutation status, suggesting that val26 may act as a susceptibility allele in the pathogenesis of TCP.
Chandak, G. R., Idris, M. M., Reddy, D. N., Bhaskar, S., Sriram, P. V. J., Singh, L. Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis. J. Med. Genet. 39: 347-351, 2002. [PubMed: 12011155] [Full Text: https://doi.org/10.1136/jmg.39.5.347]
Hassan, Z., Mohan, V., McDermott, M. F., Ali, L., Ogunkolade, W. B., Aganna, E., Cassell, P. G., Deepa, R., Azad Khan, A. K., Hitman, G. A. Pancreatitis in fibrocalculous pancreatic diabetes mellitus is not associated with common mutations in the trypsinogen gene. Diabetes Metab. Res. Rev. 16: 454-457, 2000. [PubMed: 11114105] [Full Text: https://doi.org/10.1002/1520-7560(2000)9999:9999<::aid-dmrr155>3.0.co;2-k]
Mahurkar, S., Idris, M. M., Reddy, D. N., Bhaskar, S., Rao, G. V., Thomas, V., Singh, L., Chandak, G. R. Association of cathepsin B gene polymorphisms with tropical calcific pancreatitis. Gut 55: 1270-1275, 2006. [PubMed: 16492714] [Full Text: https://doi.org/10.1136/gut.2005.087403]
Mohan, V., Chari, S. T., Hitman, G. A., Suresh, S., Madanagopalan, N., Ramachandran, A., Viswanathan, M. Familial aggregation in tropical fibrocalculous pancreatic diabetes. Pancreas 4: 690-693, 1989. [PubMed: 2813331] [Full Text: https://doi.org/10.1097/00006676-198912000-00006]
Rossi, L., Whitcomb, D. C., Ehrlich, G. D., Gorry, M. C., Parvin, S., Sattar, S., Ali, L., Azad Khan, A. K., Gyr, N. Lack of R117H mutation in the cationic trypsinogen gene in patients with tropical calcific pancreatitis from Bangladesh. Pancreas 17: 278-280, 1998. [PubMed: 9788542] [Full Text: https://doi.org/10.1097/00006676-199810000-00009]