Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation
-
Sonya Galcheva
,
Violeta Iotova
Abstract
Background:
Congenital hyperinsulinism (CHI) can present with considerable clinical heterogeneity which may be due to differences in the underlying genetic etiology. We present two siblings with hyperinsulinaemic hypoglycaemia (HH) and marked clinical heterogeneity caused by compound heterozygosity for the same two novel ABCC8 mutations.
Case presentation:
The index patient is a 3-year-old boy with hypoglycaemic episodes presenting on the first day of life. HH was diagnosed and treatment with intravenous glucose and diazoxide was initiated. Currently he has normal physical and neurological development, with occasional hypoglycaemic episodes detected following continuous fasting on treatment with diazoxide. The first-born 8-year-old sibling experienced severe postnatal hypoglycaemia, generalised seizures and severe brain damage despite diazoxide treatment. The latter was stopped at 6-months of age with no further registered hypoglycaemia. Genetic testing showed that both children were compound heterozygotes for two novel ABCC8 missense mutations p.I60N (c.179T>A) and p.G1555V (c.4664G>T).
Conclusions:
These ABCC8 missense mutations warrant further studies mainly because of the variable clinical presentation and treatment response.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The genetic studies were funded by the Medical Research Council (Grant Number 98144). SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number: 105636/Z/14/Z).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Artikel in diesem Heft
- Frontmatter
- Editorial
- Pediatric endocrinology is pediatrics is public health
- Original Articles
- Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children
- Vitamin D supplementation, the metabolic syndrome and oxidative stress in obese children
- Vitamin D status in Egyptian children with type 1 diabetes and the role of vitamin D replacement in glycemic control
- Cross-sectional analysis of universal vitamin D supplementation in former East Germany during the first year of life
- Ethnicity and incidence of congenital hypothyroidism in the capital of Macedonia
- Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy
- Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance
- Analysis of growth hormone receptor gene expression in tall and short stature children
- Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals
- Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes
- Associations between obesity, adverse behavioral patterns and cardiovascular risk factors among adolescent inhabitants of a Greek island
- Increase of body mass index (BMI) from 1.5 to 3 years of age augments the degree of insulin resistance corresponding to BMI at 12 years of age
- Case Reports
- The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency
- Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB
- Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation
- Cushing’s syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma
- Letters to the Editor
- Growth-hormone deficiency in mitochondrial disorders
- Response to Growth hormone deficiency in mitochondrial disorders
Artikel in diesem Heft
- Frontmatter
- Editorial
- Pediatric endocrinology is pediatrics is public health
- Original Articles
- Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children
- Vitamin D supplementation, the metabolic syndrome and oxidative stress in obese children
- Vitamin D status in Egyptian children with type 1 diabetes and the role of vitamin D replacement in glycemic control
- Cross-sectional analysis of universal vitamin D supplementation in former East Germany during the first year of life
- Ethnicity and incidence of congenital hypothyroidism in the capital of Macedonia
- Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy
- Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance
- Analysis of growth hormone receptor gene expression in tall and short stature children
- Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals
- Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes
- Associations between obesity, adverse behavioral patterns and cardiovascular risk factors among adolescent inhabitants of a Greek island
- Increase of body mass index (BMI) from 1.5 to 3 years of age augments the degree of insulin resistance corresponding to BMI at 12 years of age
- Case Reports
- The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency
- Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB
- Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation
- Cushing’s syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma
- Letters to the Editor
- Growth-hormone deficiency in mitochondrial disorders
- Response to Growth hormone deficiency in mitochondrial disorders
