Journal Article10.1056/NEJM199805073381904
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene.
Charles A. Stanley,Yen K. Lieu,Betty Y.L. Hsu,Alberto Burlina,Cheryl R. Greenberg,Nancy J. Hopwood,Kusiel Perlman,Barry H. Rich,Enrico Zammarchi,Mortimer Poncz +9 more
TL;DR: The hyperinsulinism-hyperammonemia syndrome is caused by mutations in the glutamate dehydrogenase gene that impair the control of enzyme activity, consistent with overactivity of the enzyme.
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Abstract: Background A new form of congenital hyperinsulinism characterized by hypoglycemia and hyperammonemia was described recently. We hypothesized that this syndrome of hyperinsulinism and hyperammonemia was caused by excessive activity of glutamate dehydrogenase, which oxidizes glutamate to α-ketoglutarate and which is a potential regulator of insulin secretion in pancreatic beta cells and of ureagenesis in the liver. Methods We measured glutamate dehydrogenase activity in lymphoblasts from eight unrelated children with the hyperinsulinism–hyperammonemia syndrome: six with sporadic cases and two with familial cases. We identified mutations in the glutamate dehydrogenase gene by sequencing glutamate dehydrogenase complementary DNA prepared from lymphoblast messenger RNA. Site-directed mutagenesis was used to express the mutations in COS-7 cells. Results The sensitivity of glutamate dehydrogenase to inhibition by guanosine 5'-triphosphate was a quarter of the normal level in the patients with sporadic hyperinsul...
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Citations
New developments in the treatment of hyperammonemia: emerging use of carglumic acid
TL;DR: Carglumic acid is an analog of N-acetylglutamate that has a direct action on carbamoyl-phosphate synthase-I that reactivation of the urea cycle and reduction of plasma ammonia levels and improves the traditional treatment, avoiding the need of hemodialysis and peritoneal dialysis.
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Hiperinsulinismo na infância: quando apenas uma dosagem de insulina não é suficiente Hyperinsulinism in Infancy and Childhood: When an Insulin Level Is Not Always Enough
Andrew A. Palladino,Michael J. Bennett,Charles A. Stanley +2 more
- 01 Jan 2008
TL;DR: A hipoglicemia in bebes e criancas pode cause convulsoes, atraso de desenvolvimento e dano cerebral permanente as mentioned in this paper.
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Genetics of congenital hyperinsulinemic hypoglycemia
TL;DR: The aim of this review is to provide an outline of the 7 different molecular mechanisms underlying this heterogeneous disease and to demonstrate that the clinical phenotype can act as a useful guide when prioritizing the order of genetic testing.
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Molecular mechanisms of congenital hyperinsulinism
TL;DR: An update on the molecular basis of CHI is provided, which shows that genetic abnormalities in HNF4A and HNF1A lead to a dual phenotype of HH in the newborn period and maturity onset-diabetes later in life.
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TL;DR: Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene, a regulator of insulin secretion, mapped to 11p15.1 by means of fluorescence in situ hybridization.
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Mutations in the Sulfonylurea Receptor Gene Are Associated with Familial Hyperinsulinism in Ashkenazi Jews
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