ABCMdb

ABCC8 p.Val607Met

Predicted by SNAP2:	A: N (66%), C: N (78%), D: D (75%), E: D (71%), F: N (57%), G: D (53%), H: D (63%), I: N (97%), K: D (63%), L: N (97%), M: N (93%), N: D (53%), P: D (75%), Q: D (63%), R: D (63%), S: N (53%), T: N (93%), W: N (53%), Y: D (66%),
Predicted by PROVEAN:	A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: N, W: D, Y: D,

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[hide] Effective treatment with oral sulfonylureas in pat... Diabetes Care. 2008 Feb;31(2):204-9. Epub 2007 Nov 19. Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S, Hattersley AT
Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations.
Diabetes Care. 2008 Feb;31(2):204-9. Epub 2007 Nov 19., [PMID:18025408]

Abstract [show]
OBJECTIVE: Neonatal diabetes can result from mutations in the Kir6.2 or sulfonylurea receptor 1 (SUR1) subunits of the ATP-sensitive K(+) channel. Transfer from insulin to oral sulfonylureas in patients with neonatal diabetes due to Kir6.2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and to compare it with Kir6.2 mutations. RESEARCH DESIGN AND METHODS: We followed 27 patients with SUR1 mutations for at least 2 months after attempted transfer to sulfonylureas. Information was collected on clinical features, treatment before and after transfer, and the transfer protocol used. We compared successful and unsuccessful transfer patients, glycemic control before and after transfer, and treatment requirements in patients with SUR1 and Kir6.2 mutations. RESULTS: Twenty-three patients (85%) successfully transferred onto sulfonylureas without significant side effects or increased hypoglycemia and did not need insulin injections. In these patients, median A1C fell from 7.2% (interquartile range 6.6-8.2%) on insulin to 5.5% (5.3-6.2%) on sulfonylureas (P = 0.01). When compared with Kir6.2 patients, SUR1 patients needed lower doses of both insulin before transfer (0.4 vs. 0.7 units x kg(-1) x day(-1); P = 0.002) and sulfonylureas after transfer (0.26 vs. 0.45 mg x kg(-1) x day(-1); P = 0.005). CONCLUSIONS: Oral sulfonylurea therapy is safe and effective in the short term in most patients with diabetes due to SUR1 mutations and may successfully replace treatment with insulin injections. A different treatment protocol needs to be developed for this group because they require lower doses of sulfonylureas than required by Kir6.2 patients.

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54 Doses Table 1-Clinical characteristics of patients with SUR1 mutations according to success of treatment with sulfonylureas Characteristic All patients Patients with successful sulfonylurea treatment Patients with unsuccessful sulfonylurea treatment P* n 27 23 4 Mutation (number of patients) NA V86G†, P45L/G1401R- (2)†, D209E (3)†, T229I/V1523L†, Q211K†, V86A (2)†, E1507G, V215I/V607M, E208K/Y263D†, R1380L (2)‡, D212I (3)§, T229I/T229I‡, R1183W§, L225P†, R826W, and D209N F132L (2)†, F132V†, and N72S† (mosaic). Login to comment
56 Doses Table 1-Clinical characteristics of patients with SUR1 mutations according to success of treatment with sulfonylureas Characteristic All patients Patients with successful sulfonylurea treatment Patients with unsuccessful sulfonylurea treatment P* n 27 23 4 Mutation (number of patients) NA V86Gߤ, P45L/G1401R- (2)ߤ, D209E (3)ߤ, T229I/V1523Lߤ, Q211Kߤ, V86A (2)ߤ, E1507G, V215I/V607M, E208K/Y263Dߤ, R1380L (2)ߥ, D212I (3)&#a7;, T229I/T229Iߥ, R1183W&#a7;, L225Pߤ, R826W, and D209N F132L (2)ߤ, F132Vߤ, and N72Sߤ (mosaic). Login to comment

[hide] KATP channel mutations in infants with permanent d... Pediatr Diabetes. 2012 Jun;13(4):322-5. doi: 10.1111/j.1399-5448.2011.00824.x. Epub 2011 Oct 10. Rubio-Cabezas O, Flanagan SE, Damhuis A, Hattersley AT, Ellard S
KATP channel mutations in infants with permanent diabetes diagnosed after 6 months of life.
Pediatr Diabetes. 2012 Jun;13(4):322-5. doi: 10.1111/j.1399-5448.2011.00824.x. Epub 2011 Oct 10., [PMID:21981029]

Abstract [show]
BACKGROUND/OBJECTIVE: Mutations in the K(ATP) channel genes are the commonest cause of permanent neonatal diabetes. Most patients obtain optimal glycemic control on sulfonylurea treatment. Genetic testing is currently recommended for all infants diagnosed before 6 months of age. We aimed to explore the prevalence of K(ATP) channel diabetes in infants presenting between 6 and 12 months. METHODS: The KCNJ11 and ABCC8 genes were sequenced in 115 infants with permanent diabetes diagnosed between 6 and 12 months and in 405 patients presenting before 6 months. RESULTS: Mutations in either gene were identified in 197 patients diagnosed before 6 months (48.6%), three infants diagnosed between 6 and 9 months (4.2%) and none of those diagnosed after 9 months. Two patients diagnosed after 6 months were successfully transferred from insulin to sulfonylureas. CONCLUSION: K(ATP) channel mutations are an uncommon cause of diabetes in infants presenting after 6 months. However, given the potential clinical benefit from identifying a K(ATP) channel mutation, we recommend that K(ATP) mutation testing should be routinely extended to infants diagnosed up to 9 months.

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46 A third Caucasian female patient was found to be a compound heterozygote for two mutations in ABCC8; V215I (c.643G>A) and V607M (c.1819G>A). Login to comment