Congenital hyperinsulinism in a newborn with a novel homozygous mutation (p.Q392H) in the ABCC8 gene

AbstractBackground:Congenital hyperinsulinism results in refractory hypoglycemia. If a therapy with diazoxide has been unresponsive this has been treated by subtotal pancreatectomy in the past. This therapeutic option poses an increased risk of developing diabetes at a later stage. There have been a few case reports on the use of sirolimus in such situations in the recent past.Case presentation:Our patient was started on sirolimus very early, on day 29 of life and at the age of 14 months is doing well on sirolimus therapy. His growth and development have been good and he has not had any major complications so far. Genetic testing showed a novelKCNJ11homozygous mutation on next generation sequencing and the parents were heterozygous carriers.Conclusions:We report the successful use of sirolimus in the management of diazoxide unresponsive congenital hyperinsulinism with diffuse pancreatic involvement. We believe this is the youngest patient to be initiated on sirolimus so far.

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A compound heterozygous mutation of ABCC8 gene causing a diazoxide-unresponsive congenital hyperinsulinism with an atypical form: Not a focal lesion in the pancreas reported by 18F-DOPA-PET/CT scan

Gene ◽

10.1016/j.gene.2015.07.012 ◽

2015 ◽

Vol 572 (2) ◽

pp. 222-226 ◽

Cited By ~ 1

Author(s):

Wen Zhang ◽

Li Liu ◽

Zhe Wen ◽

Jing Cheng ◽

Cuiling Li ◽

...

Keyword(s):

Ct Scan ◽

Compound Heterozygous Mutation ◽

Focal Lesion ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Congenital Hyperinsulinism ◽

Atypical Form ◽

Abcc8 Gene ◽

Pet Ct ◽

Pet Ct Scan

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Novel Compound Heterozygous Variants of the ABCC8 Gene Warrant Identification of Pancreatic Histology in Infant with Diazoxide-unresponsive Congenital Hyperinsulinism

Children ◽

10.3390/children8100836 ◽

2021 ◽

Vol 8 (10) ◽

pp. 836

Author(s):

Rana Al Balwi ◽

Dalal Bubshait ◽

Raed Al Nefily ◽

Omar Al Ghamdi

Keyword(s):

Autosomal Recessive ◽

Severe Hypoglycemia ◽

Katp Channels ◽

Compound Heterozygous ◽

Congenital Hyperinsulinism ◽

Abcc8 Gene ◽

Genes Encoding ◽

One Year ◽

The One ◽

Compound Heterozygous Variants

Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion, resulting in severe hypoglycemia. Mutations in the ABCC8 and KCNJ11 genes encoding KATP channels in beta cells of the pancreas are common among patients with CHI. Autosomal recessive CHI with diffuse involvement is the most common type of CHI among Saudi patients. It is relatively common for patients with autosomal recessive CHI to be medically unresponsive and undergo pancreatectomy. In this case report, we describe novel compound heterozygous variants in the ABCC8 gene in a Saudi infant that caused diazoxide-unresponsive CHI. The variants included a monoallelic paternally inherited variant that has been previously reported to cause a focal form of CHI and a maternally inherited variant of unknown significance (VUS). The severity of CHI in this patient was mild over the one-year follow-up period, with a near-optimal glycemic response on a low dose of octreotide. We suspected an atypical subtype of histological involvement in the patient. In this report, we highlight the phenotypic spectrum of novel compound heterozygous variants in a patient with CHI and consider that the report can help establish the pathogenicity of the VUS.

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Genotyping of ABCC8, KCNJ11, and HADH in Iranian Infants with Congenital Hyperinsulinism

Case Reports in Endocrinology ◽

10.1155/2021/8826174 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Somayyeh Hashemian ◽

Reza Jafarzadeh Esfehani ◽

Siroos Karimdadi ◽

Nosrat Ghaemi ◽

Peyman Eshraghi ◽

...

Keyword(s):

Mutational Analysis ◽

Genetic Diagnosis ◽

Case Series ◽

Missense Variant ◽

Congenital Hyperinsulinism ◽

Biochemical Tests ◽

Functional Studies ◽

Pathogenic Variants ◽

Abcc8 Gene ◽

Kcnj11 Gene

Background. Congenital hyperinsulinism (CHI) is a heterogeneous disease with various underlying genetic causes. Among different genes considered effective in the development of CHI, ABCC8, KCNJ11, and HADH genes are among the important genes, especially in a population with a considerable rate of consanguineous marriage. Mutational analysis of these genes guides clinicians to better treatment and prediction of prognosis for this rare disease. The present study aimed to evaluate genetic variants in ABCC8, KCNJ11, and HADH genes as causative genes for CHI in the Iranian population. Methods. The present case series took place in Mashhad, Iran, within 11 years. Every child who had a clinical phenotype and confirmatory biochemical tests of CHI enrolled in this study. Variants in ABCC8, KCNJ11, and HADH genes were analyzed by the polymerase chain reaction and sequencing in our patients. Results. Among 20 pediatric patients, 16 of them had variants in ABCC8, KCNJ11, and HADH genes. The mean age of genetic diagnosis was 18.6 days. A homozygous missense (c.2041-21G > A) mutation in the ABCC8 gene was seen in three infants. Other common variants were frameshift variants (c.3438dup) in the ABCC8 gene and a missense variant (c.287-288delinsTG) in the KCNJ11 gene. Most of the variants in our population were still categorized as variants of unknown significance and only 7 pathogenic variants were present. Conclusion. Most variants were located in the ABCC8 gene in our population. Because most of the variants in our population are not previously reported, performing further functional studies is warranted.

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A Case Report on Congenital Hyperinsulinism

Journal of Neonatology ◽

10.1177/0973217920933085 ◽

2020 ◽

Vol 34 (3) ◽

pp. 170-171

Author(s):

Sandip Pagdar ◽

Kunj Jobanputra ◽

Mohit Sahni

Keyword(s):

Case Report ◽

Surgical Treatment ◽

Genetic Study ◽

Homozygous Deletion ◽

Congenital Hyperinsulinism ◽

Heterozygous Deletion ◽

Partial Pancreatectomy ◽

Initial Management ◽

Abcc8 Gene ◽

Gene Study

Introduction: Congenital hyperinsulinism (CH) is the most common reason for persistent hypoglycemia in neonates. Insulin levels increased inappropriately in the presence of hypoglycemia. Initial management is nonsurgical, but if it fails then partial pancreatectomy is done, which is a surgical procedure. Objective: To report newborn with CH and update medical and/or surgical treatment. Case report: It is reporting of a term newborn with severe symptomatic hypoglycemia not responding to medical treatment. Gene study was done—ABCC8 gene has been identified as homozygous deletion of exon 13 and parents ger08Y—showing heterozygous deletion of exon 13. Genetic study was consistent with focal CH. Discussion: This report presents diagnosis and clinical features of CH.

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