scholarly journals Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Maryam Razzaghy-Azar ◽  
Saeedeh Saeedi ◽  
Sepideh Borhan Dayani ◽  
Samaneh Enayati ◽  
Farzaneh Abbasi ◽  
...  
Keyword(s):  
Large Cohort ◽  
Genetic Mutations ◽  
Congenital Hyperinsulinism ◽  
Iranian Patients

scholarly journals Comprehensive genotype‐phenotype correlation in AP ‐4 deficiency syndrome; Adding data from a large cohort of Iranian patients

2020 ◽  
Vol 99 (1) ◽  
pp. 187-192
Author(s):  
Maryam Beheshtian ◽  
Tara Akhtarkhavari ◽  
Sepideh Mehvari ◽  
Marzieh Mohseni ◽  
Zohreh Fattahi ◽  
...  
Keyword(s):  
Deficiency Syndrome ◽  
Large Cohort ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Iranian Patients

scholarly journals Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different clinical centers

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Alena Welters ◽  
Christian Lerch ◽  
Sebastian Kummer ◽  
Jan Marquard ◽  
Burak Salgin ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Descriptive Analysis ◽  
Large Cohort ◽  
Congenital Hyperinsulinism

scholarly journals A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism

2021 ◽  
Vol 11 ◽  
Author(s):  
Julie Siersbæk ◽  
Annette Rønholt Larsen ◽  
Mads Nybo ◽  
Henrik Thybo Christesen
Keyword(s):  
Detection Limit ◽  
Clinical Diagnosis ◽  
Area Under The Curve ◽  
Genetic Mutations ◽  
Congenital Hyperinsulinism ◽  
Operating Characteristics ◽  
Normal Range ◽  
Lower Detection Limit ◽  
Ketotic Hypoglycemia ◽  
Lower Detection

BackgroundThe diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12–18 pmol/L (2–3 mU/L).ObjectiveTo evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI.MethodsDiagnostic fasting tests, performed without medication or i.v.-glucose, were investigated in children with a clinical diagnosis of CHI, or idiopathic ketotic hypoglycemia (IKH). The CHI diagnosis was either clinical or by the alternative, p-insulin-free criteria; hypoglycemia plus disease-causing genetic mutations and/or CHI-compatible pancreatic histopathology. We included diagnostic p-insulin samples with simultaneous p-glucose <3.2 mmol/L and used a sensitive insulin assay (Cobas e411 immunoassay analyzer; lower detection limit 1.2 pmol/L; normal range 15.1–147.1 pmol/L). Receiver operating characteristics area under the curve (ROC AUC) values and optimal cut-offs were analyzed for the performance of p-insulin to diagnose CHI.ResultsIn 61 CHI patients, the median (range) p-insulin was 76.5 (17–644) pmol/L compared to 1.5 (1.5–7.7) pmol/L in IKH patients (n=15). The ROC AUC was 1.0 for the diagnosis of CHI defined both by the clinical diagnosis (n=61) and by alternative criteria (n=57). The optimal p-insulin cut-offs were 12.3 pmol/L, and 10.6 pmol/L, at p-glucose <3.2 mmol/L (n=61), and <3.0 mmol/L (n=49), respectively.ConclusionsThe sensitive insulin assay performed excellent in diagnosing CHI with optimal p-insulin cut-offs at 12.3 pmol/L (2.0 mU/L), and 10.6 pmol/L (1.8 mU/L), at p-glucose <3.2 mmol/L, and <3.0 mmol/L, respectively. A sensitive insulin assay may serve to simplify the diagnosis of CHI.

scholarly journals Clinical and histological heterogeneity of congenital hyperinsulinism due to paternally inherited heterozygous ABCC8/KCNJ11 mutations

2014 ◽  
Vol 171 (6) ◽  
pp. 685-695 ◽  
Author(s):  
Ved Bhushan Arya ◽  
Maria Guemes ◽  
Azizun Nessa ◽  
Syeda Alam ◽  
Pratik Shah ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Relative Proportion ◽  
Retrospective Chart Review ◽  
Ct Scanning ◽  
Large Cohort ◽  
Congenital Hyperinsulinism ◽  
Diffuse Disease ◽  
Positron Emission ◽  
Pet Ct ◽  
Histological Heterogeneity

ContextCongenital hyperinsulinism (CHI) has two main histological types: diffuse and focal. Heterozygous paternally inherited ABCC8/KCNJ11 mutations (depending upon whether recessive or dominant acting and occurrence of somatic maternal allele loss) can give rise to either phenotype. However, the relative proportion of these two phenotypes in a large cohort of CHI patients due to paternally inherited heterozygous ABCC8/KCNJ11 mutations has not been reported.ObjectiveThe purpose of this study is to highlight the variable clinical phenotype and to characterise the distribution of diffuse and focal disease in a large cohort of CHI patients due to paternally inherited heterozygous ABCC8/KCNJ11 mutations.DesignA retrospective chart review of the CHI patients due to heterozygous paternally inherited ABCC8/KCNJ11 mutations from 2000 to 2013 was conducted.ResultsPaternally inherited heterozygous ABCC8/KCNJ11 mutations were identified in 53 CHI patients. Of these, 18 (34%) either responded to diazoxide or resolved spontaneously. Fluorine-18 l-3, 4-dihydroxyphenylalanine positron emission tomography computerised tomography (18F DOPA–PET CT) scanning in 3/18 children showed diffuse disease. The remaining 35 (66%) diazoxide-unresponsive children either had pancreatic venous sampling (n=8) or 18F DOPA–PET CT (n=27). Diffuse, indeterminate and focal disease was identified in 13, 1 and 21 patients respectively. Two patients with suspected diffuse disease were identified to have focal disease on histology.ConclusionsPaternally inherited heterozygous ABCC8/KCNJ11 mutations can manifest as a wide spectrum of CHI with variable 18F DOPA–PET CT/histological findings and clinical outcomes. Focal disease was histologically confirmed in 24/53 (45%) of CHI patients with paternally inherited heterozygous ABCC8/KCNJ11 mutations.

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