Permanent neonatal diabetes caused by a novel mutation
Vandana Jain1, Sarah E Flanagan, Sian Ellard
1Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. drvandanajain@gmail.com
Indian Pediatrics
|July 17, 2012
Summary
Permanent neonatal diabetes mellitus (PNDM) typically results from activating mutations. This case reveals compound heterozygous mutations in ABCC8, causing both PNDM and hyperinsulinemia in an infant from unaffected parents.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Permanent form of neonatal diabetes mellitus (PNDM) is often caused by activating mutations in KCNJ11 or ABCC8 genes.
- These genes encode subunits of the pancreatic b cell KATP channel, crucial for insulin secretion.
Observation:
- A case study of an infant diagnosed with PNDM is presented.
- The infant exhibited compound heterozygous mutations in the ABCC8 gene.
Findings:
- One ABCC8 mutation predicted a gain of function, leading to neonatal diabetes.
- The other ABCC8 mutation predicted a loss of function, associated with hyperinsulinemia.
Implications:
- This case highlights a novel genetic mechanism for PNDM and hyperinsulinemia.
- Understanding these compound mutations is vital for accurate diagnosis and genetic counseling.
- It expands the known spectrum of KATP channelopathies and their clinical manifestations.
More Related Videos
Related Concept Videos
01:20Pathophysiology of Diabetes
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...
01:20Inborn Errors of Metabolism
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
01:26Diabetes Mellitus: Introduction
Diabetes mellitus consists of chronic metabolic disorders characterized by persistent hyperglycemia. This elevated blood glucose results from defects in insulin secretion, impaired insulin action, or both. Insulin, produced by pancreatic β-cells, is essential for maintaining glucose homeostasis by facilitating cellular glucose uptake for energy or storage. Disruptions in insulin production or function lead to glucose accumulation in the bloodstream, causing the clinical features and long-term...
01:22Diabetes Mellitus: Type 2 and Gestational
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
01:26Type II Diabetes I: Introduction
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...
01:22Diabetes Mellitus: Overview and Type I Subtype
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...