Diagnosis of congenital Hyperinsulinism can occur not only in infancy but also in later age: a new flow chart from a single center experience

Abstract

Background Congenital Hyperinsulinism typically occurs with a neonatal hypoglycemia but can appear even in childhood or in adolescence with different types of glucose metabolism derangements. Current diagnostic algorithms don’t take into account cases with a late presentation. Patients and methods Clinical and laboratory data of twenty-two subjects diagnosed at Federico II University of Naples have been described: patients have been divided according to the molecular defect into channel defects, metabolic defects and unidentified molecular defects. A particular focus has been made on three cases with a late presentation. Results and conclusions Late presentation cases may not be identified by previous diagnostic algorithms. Consequently, it seems appropriate to design a new flow-chart starting from the age of presentation, also considering that late presentation cases can show glucose metabolism derangements other than hypoglycaemic crises such as diabetes, glucose intolerance, postprandial hypoglycaemia and gestational diabetes.

An Overview of Hypoglycemia in Children Including a Comprehensive Practical Diagnostic Flowchart for Clinical Use

“…These forms usually develop sporadically in a patient carrying a recessive ABCC8/KCNJ11 paternally inherited mutation, when a somatic loss of the maternal allele occurs ("double hit"). ABCC8 mutations can cause phenotypes who switch from HY in infancy to hyperglycemia in adolescence and even adulthood (39)(40)(41). Late onset forms are mostly linked to dominant mutations of ABCC8/KCNJ11 genes or to activating mutation of GCK gene (40).…”

“…ABCC8 mutations can cause phenotypes who switch from HY in infancy to hyperglycemia in adolescence and even adulthood ( 39 – 41 ). Late onset forms are mostly linked to dominant mutations of ABCC8/KCNJ11 genes or to activating mutation of GCK gene ( 40 ). CH diagnosis may be suspected at any insulin concentration detectable in a hypoglycemic plasma sample thus as a marker of inappropriate insulin secretion ( 1 , 42 ).…”

“…Indirect signs of this phenomenon are the absence of ketonemia (excepted for HADH deficit) and fatty acidemia. Adjunctive diagnostic criteria for CH could be a positive response to glucagon or octreotide injection (glucose levels >1.5 mmol/L) and the need for more than 8 mg/kg/min of glucose infusion to maintain euglycemia ( 1 , 32 , 38 , 40 , 41 ). Some authors ( 42 ) have proposed a classification of CH diagnostic criteria as reported in the Table 5 .…”

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

“…CHI diagnostic algorithms start from the metabolic evaluation followed by molecular investigation and genotyping. Although genetic analysis is the most useful test in hyperinsulinism diagnostic approach, specific radiological modalities such as 18-F-DOPA positron emission tomography (PET) scan are also used to specify lesions [4]. Variants in some specific genes that regulate insulin secretion are considered to be responsible for the development of CHI.…”