A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8
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Abstract
Background
Congenital hyperinsulinism (CHI) occurs due to an unregulated insulin secretion from the pancreatic β-cells resulting in hypoglycaemia. Causative mutations in multiple genes have been reported. Phenotypic variability exists both within and between different genetic subgroups.
Case presentation
A male infant born at 35+6 weeks’ gestation with a birth weight of 4.3 kg [+3.6 standard deviation score (SDS)] had recurrent hypoglycaemic episodes from birth. Biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and the dose was progressively increased to maintain euglycaemia. His father was slim and had been diagnosed with type 2 diabetes in his 30s. Sequence analysis identified a heterozygous hepatocyte nuclear factor 4 alpha (HNF4A) mutation (p.Arg245Pro, c.734G>C) and compound heterozygous ABCC8 mutations (p.Gly92Ser, c.274G>A and p.Ala1185Val, c.3554C>T) in the patient. The p.Ala1185Val ABCC8 mutation was inherited from his unaffected mother and the p.Arg245Pro HNF4A and p.Gly92Ser ABCC8 mutations from his father. All three mutations were predicted to be pathogenic. Identification of the HNF4A mutation in the father established a diagnosis of maturity-onset diabetes of the young (MODY), which enabled medication change resulting in improved glycaemic control.
Conclusions
We report a rare patient with CHI due to dual genetic aetiology. Although he is currently responsive to the maximum dose of diazoxide, the long-term prognosis remains unclear.
Acknowledgements
None.
Author contributions: LA and DG collected the data, wrote and revised the draft. JH, SF and MD contributed to the revision of the draft. SS supervised the study and revised the final draft.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(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.
Statement of ethics: Full parental consent was obtained for publication.
Conflicts of interest: None.
ESPE/PES Members: Senthil Senniappan and Dinesh Giri.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Original Articles
- Improved adherence and growth outcomes with jet-delivered growth hormone
- Validation of the Greek version of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire
- Growth hormone deficiency in children with antenatal Bartter syndrome
- Physical growth and development characteristics of children with Williams syndrome aged 0–24 months in Zhejiang Province
- Adiposity and adipocytokines: the moderator role of cardiorespiratory fitness and pubertal stage in girls
- Serum omentin-1 levels in obese children
- A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing
- Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature
- Studying the effect of large neutral amino acid supplements on oxidative stress in phenylketonuric patients
- The effect of therapy on plasma ghrelin and leptin levels, and appetite in children with iron deficiency anemia
- The effect of PKU diet on the maternal quality of life and social discrimination in relation to their educational status and place of living
- Evaluating the four most important salivary sex steroids during male puberty: testosterone best characterizes pubertal development
- Case Reports
- Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing
- A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8
- Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature
Artikel in diesem Heft
- Frontmatter
- Original Articles
- Improved adherence and growth outcomes with jet-delivered growth hormone
- Validation of the Greek version of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire
- Growth hormone deficiency in children with antenatal Bartter syndrome
- Physical growth and development characteristics of children with Williams syndrome aged 0–24 months in Zhejiang Province
- Adiposity and adipocytokines: the moderator role of cardiorespiratory fitness and pubertal stage in girls
- Serum omentin-1 levels in obese children
- A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing
- Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature
- Studying the effect of large neutral amino acid supplements on oxidative stress in phenylketonuric patients
- The effect of therapy on plasma ghrelin and leptin levels, and appetite in children with iron deficiency anemia
- The effect of PKU diet on the maternal quality of life and social discrimination in relation to their educational status and place of living
- Evaluating the four most important salivary sex steroids during male puberty: testosterone best characterizes pubertal development
- Case Reports
- Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing
- A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8
- Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature
