Congenital hyperinsulinism due to compound heterozygous mutations in ABCC8 responsive to diazoxide therapy

Taylor-Miller, Tashunka; Houghton, Jayne; Munyard, Paul; Kumar, Y; Puvirajasinghe, Clinda; Giri, Dinesh

doi:10.1515/jpem-2019-0457

Cited by 7 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, heterozygous carriers of a mutation in the ABCC8 gene require long-term monitoring, as they present an increased risk for diabetes mellitus [39,40].…”

Section: Genetic Counselingmentioning

confidence: 99%

Genetic Heterogeneity Correlated with Phenotypic Variability in Congenital Hyperinsulinism Caused by Mutation in ABCC8 Gene Associated with Early‐Onset Persistent Neonatal Hypoglycemia

Butnariu,

Bizim,

Păduraru

et al. 2024

Preprint

View full text Add to dashboard Cite

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

show abstract

“…In addition, heterozygous carriers of a mutation in the ABCC8 gene require long-term monitoring, as they present an increased risk for diabetes mellitus [39,40].…”

Section: Genetic Counselingmentioning

confidence: 99%

Genetic Heterogeneity Correlated with Phenotypic Variability in Congenital Hyperinsulinism Caused by Mutation in ABCC8 Gene Associated with Early‐Onset Persistent Neonatal Hypoglycemia

Butnariu,

Bizim,

Păduraru

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, heterozygous carriers of a mutation in the ABCC8 gene require long-term monitoring, as they present an increased risk for diabetes mellitus [43,48].…”

Section: Genetic Counselingmentioning

confidence: 99%

Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability

Butnariu,

Bizim,

Păduraru

et al. 2024

IJMS

View full text Add to dashboard Cite

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

show abstract

“…The consequent closure of the K-ATP channels results in a blockage of potassium entry into the cell with a gradual depolarization, opening of voltage-gated calcium channels and exocytosis of insulin granules [ 31 ]. CH is associated with over 12 different genetic loci and the most frequent are inactivating mutations of ABCC8 and KCNJ11 [ 32 ], which encode SUR1 and KIR6.2 subunits, with a consequent lack of channels on the beta-cell membrane or channels impaired function and dysregulated insulin secretion [ 33 , 34 ]. Other inactivating mutations include Hepatic Nuclear Factor 4 Alpha (HNF4A) and Hepatic Nuclear Factor 1 Alpha (HNF1A).…”

Section: Etiologymentioning

confidence: 99%

Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives

et al. 2023

View full text Add to dashboard Cite

Hypoglycemia is due to defects in the metabolic systems involved in the transition from the fed to the fasting state or in the hormone control of these systems. In children, hypoglycemia is considered a metabolic-endocrine emergency, because it may lead to brain injury, permanent neurological sequelae and, in rare cases, death. Symptoms are nonspecific, particularly in infants and young children. Diagnosis is based on laboratory investigations during a hypoglycemic event, but it may also require biochemical tests between episodes, dynamic endocrine tests and molecular genetics. This narrative review presents the age-related definitions of hypoglycemia, its pathophysiology and main causes, and discusses the current diagnostic and modern therapeutic approaches.

show abstract

Congenital hyperinsulinism due to compound heterozygous mutations in ABCC8 responsive to diazoxide therapy

Cited by 7 publications

References 17 publications

Genetic Heterogeneity Correlated with Phenotypic Variability in Congenital Hyperinsulinism Caused by Mutation in ABCC8 Gene Associated with Early‐Onset Persistent Neonatal Hypoglycemia

Genetic Heterogeneity Correlated with Phenotypic Variability in Congenital Hyperinsulinism Caused by Mutation in ABCC8 Gene Associated with Early‐Onset Persistent Neonatal Hypoglycemia

Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability

Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives

Contact Info

Product

Resources

About