ABCMdb

PMID: 23926410

Saito-Hakoda A, Yorifuji T, Kanno J, Kure S, Fujiwara I
Nateglinide is Effective for Diabetes Mellitus with Reactive Hypoglycemia in a Child with a Compound Heterozygous ABCC8 Mutation.
Clin Pediatr Endocrinol. 2012 Jul;21(3):45-52. doi: 10.1297/cpe.21.45. Epub 2012 Jul 25., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC8 p.Arg1420His Sequencing of the ABCC8 identified a compound heterozygous mutation (R1420H/F591fs604X), suggesting that this mutation may alter regulation of insulin secretion with advancing age, leading to diabetes mellitus with reactive hypoglycemia from hyperinsulinism. Therefore, long-term follow-up and periodic OGTTs are important for early detection of insulin dysregulation in congenital hyperinsulinism patients carrying the ABCC8 mutation, even though hypoglycemia resolves spontaneously during infancy. Furthermore, nateglinide may be useful therapeutically in the treatment of not only diabetes mellitus but also reactive hypoglycemia. Login to comment 50 ABCC8 p.Arg1420His ABCC8 analysis identified a compound heterozygous mutation, c.4259G>A (p.R1420H; exon35) and c.1773delC (p.F591fs604X; exon12). Login to comment 53 ABCC8 p.Arg1420His Discussion The characteristic clinical course in our case is that a patient carrying a compound heterozygous ABCC8 mutation (R1420H/ F591fs604X) was born macrosomic with severe hypoglycemia in the neonatal period followed by development of diabetes mellitus accompanied by repeated reactive hypoglycemia in childhood. Login to comment 60 ABCC8 p.Glu1506Lys Huopio et al. reported that a heterozygous E1506K mutation in ABCC8 caused CHI in infancy, loss of insulin secretory capacity in early childhood and diabetes mellitus in middle age (7, 13). Login to comment 62 ABCC8 p.Arg370Ser On the other hand, Abdulhadi-Atwan et al. reported diabetes mellitus development at 10.5 yr after mild hypoglycemia during infancy in a patient carrying a heterozygous R370S mutation in ABCC8 (8). Login to comment 73 ABCC8 p.Arg1420His Thepatientwedescribedcarriedacompound heterozygous ABCC8 mutation, c4259G>A (R1420H; exon 35, paternal) and c1773 delC (F591fs604X; exon 12, maternal). Login to comment 77 ABCC8 p.Arg1420His The patient (indicated by the arrow) carried a compound heterozygous ABCC8 mutation, c4259G>A (p.R1420H; exon 35, paternal) and c1773 delC (p.F591fs604X; exon 12, maternal). Login to comment 79 ABCC8 p.Arg1420Cys (NBF2) of SUR1, and homozygous missense mutation R1420C is reported in Japanese CHI siblings(22).Althoughtheywerebornmacrosomic and developed hypoglycemia soon after birth, hypoglycemia resolve spontaneously after 3 mo ofage.FunctionalanalysisofthemutantR1420C SUR1 showed lower expression of the mutant channelandreducedaffinityofNFB2forMgADP that might leadtotheenhancedinsulinsecretion (23). Login to comment 80 ABCC8 p.Arg1420His Although the substituted amino acid was different and the mutation was compound heterozygous in our case, the R1420H mutation may also impair K-ATP channel activity. Login to comment