ABCMdb

PMID: 20042013

Vieira TC, Bergamin CS, Gurgel LC, Moises RS
Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation.
Pediatr Diabetes. 2010 Nov;11(7):505-8. doi: 10.1111/j.1399-5448.2009.00626.x., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC8 p.Glu1506Lys ABCC8 p.Glu1506Lys Pediatric Diabetes 2010: 11: 505-508 doi: 10.1111/j.1399-5448.2009.00626.x All rights reserved (c) 2009 John Wiley & Sons A/S Pediatric Diabetes Case Report Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation Vieira TC, Bergamin CS, Gurgel LC, Mois´es RS. Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation. Login to comment 7 ABCC8 p.Glu1506Lys Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood. Login to comment 11 ABCC8 p.Glu1506Lys Our data corroborate the hypothesis that the dominant E1506K ABCC8 mutation, responsible for CHI, predisposes to the development of glucose intolerance and diabetes later in life. Login to comment 23 ABCC8 p.Glu1506Lys These patients carried the inactivating heterozygous ABCC8 E1506K mutation (8, 9). Login to comment 25 ABCC8 p.Glu1506Lys Here, we report a family carrying the E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes mellitus in adulthood. Login to comment 37 ABCC8 p.Glu1506Lys When the child was one year old, the molecular studies of ABCC8 revealed the E1506K mutation, and octreotide was switched to diazoxide 10 mg/kg/day. Login to comment 52 ABCC8 p.Glu1506Lys 506 CHI and E1506K SUR1 mutation Fig. 1. Login to comment 54 ABCC8 p.Glu1506Lys Solid circles correspond to the affected mother and daughter; (B) Partial sequence chromatogram of exon 37 of ABCC8 gene showing the heterozygous mutation 4516G>A (E1506K) (a) and wild-type sequence (b). Login to comment 57 ABCC8 p.Glu1506Lys Results showed that the mother harbors a de novo ABCC8 E1506K mutation that was transmitted to her daughter (Fig. 1). Login to comment 58 ABCC8 p.Glu1506Lys Discussion The heterozygous missense mutation E1506K in ABCC8 gene has been previously identified among patients with CHI (8, 12). Login to comment 59 ABCC8 p.Glu1506Lys In vitro electrophysiological functional studies of this mutation showed that E1506K mutant KATP channels were insensitive to metabolic inhibition, but were activated by diazoxide (8). Login to comment 60 ABCC8 p.Glu1506Lys These findings are consistent with the ability of diazoxide, but not low-blood glucose, to inhibit insulin secretion in E1506K mutation carriers. Login to comment 65 ABCC8 p.Glu1506Lys Reports of CHI as a result of the E1506K mutation also describe variable degrees of hypoglycemia in the affected patients, beginning at the neonatal period or later (8, 12). Login to comment 74 ABCC8 p.Glu1506Lys Huopio et al. studied a large Finish pedigree carrying the dominant E1506K mutation and found that the patients had hyperinsulinism in infancy but were predisposed to develop gestational diabetes, glucose intolerance, and type 2 diabetes in adulthood. Login to comment 75 ABCC8 p.Glu1506Lys Insulin secretion decreased linearly with age in E1506K carriers, Pediatric Diabetes 2010: 11: 505-508 507 independently of their glucose tolerance status (9). Login to comment 76 ABCC8 p.Arg370Ser A recent report identified a de novo heterozygous inactivating ABCC8 mutation (R370S) in a girl who presented CHI early in life, but developed insulinopenic antibody-negative diabetes and obesity later in childhood (10). Login to comment 80 ABCC8 p.Glu1506Lys However, so far, there are no studies showing elevated β cell intracellular calcium concentrations in E1506K carriers. Login to comment 84 ABCC8 p.Glu1506Lys In the present report, the fact that the mother of the index patient had hypoglycemia in childhood but developed gestational diabetes, impaired glucose tolerance and diabetes mellitus in adulthood, reinforces the hypothesis that the dominant E1506K ABCC8 mutation may have an important role in the progressive impairment of the β-cell function. Login to comment