Aim: ATP-sensitive potassium channels are important regulators of insulin secretion. They consist of four sulphonylurea receptor (encoded by ABCC8) and four inwardly rectifying protein (encoded by KCNJ11) subunits. Activating ABCC8 mutations lead to decreased insulin secretion and to diabetes. Wide phenotype variability is associated with single ABCC8 mutations, ranging from transient or permanent neonatal diabetes (ND) with or without developmental delay (DEND syndrome) to very mild phenotypes. This report describes the case of a Caucasian infant diagnosed with ND at the age of 2 months due to a novel ABCC8 missense mutation.
Methods: ABCC8 was analyzed by sequence analysis. The mutation was present in the patient and her family and was found to be associated with phenotypes ranging from ND to asymptomatic impaired fasting glucose (IFG).
Results: A novel His863Tyr ABCC8 mutation was identified in a 2-month-old girl diagnosed with ND. After an initial insulin treatment, treatment with glibenclamide was initiated and the treatment with insulin discontinued. The same mutation was found in her father, who had been fortuitously diagnosed with diabetes and had an HbA(1c) level of 9% (74.8 mmol/mol). The patient's brother and mother both had normal fasting glucose, and were not found to be carriers of the mutation. However, the same mutation was found in her grandmother, who had been asymptomatic and discovered IFG (6.9 mmol/L) with an HbA(1c) of 6.8% (50.8 mmol/mol).
Conclusion: This case describes a novel ABCC8 mutation and offers a further illustration of the highly variable phenotypes associated with an identical mutation present across three generations.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.diabet.2011.12.001 | DOI Listing |
JCEM Case Rep
December 2024
Endocrinology Research Centre, Moscow, 117036, Russian Federation.
Congenital hyperinsulinism (CHI) is a rare hereditary disease characterized by the development of hypoglycemia in both infants and adult patients. CHI may be induced by activating mutations in the () gene, which encodes the human glucokinase enzyme. This form of the disease is characterized by considerable phenotypic heterogeneity and may vary in severity of its course.
View Article and Find Full Text PDFNeuroendocrinology
November 2024
World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russian Federation.
J Clin Endocrinol Metab
November 2024
Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Background: Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY) and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1-4.2% of all diabetes cases.
View Article and Find Full Text PDFSci Rep
October 2024
Institute for Comprehensive Medical Sciences, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
BMJ Case Rep
September 2024
Paediatrics, MS Ramaiah Medical College, Bangalore, Karnataka, India.
Familial hyperinsulinaemic hypoglycaemia-1 arises from mutations within the genes of pancreatic beta cells, resulting in unregulated insulin secretion from pancreatic beta cells. A 4.06 kg female neonate, born to a second-degree consanguineously married couple, presented with repeated asymptomatic hypoglycaemia.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!