Genetic perspectives on childhood monogenic diabetes: Diagnosis, management, and future directions

Table 1 General classification of diabetes

Type of diabetes	Causes and characteristics
Type 1	Insulin insufficiency is caused by the autoimmune destruction of β-cells
Type 2	Insulin resistance and inadequate secretion of insulin
Gestational	Diagnosed in 2nd or 3rd trimester of pregnancy
Monogenic	Due to genetic variation in one or multiple genes leading to maternally-inherited diabetes and deafness, mature-onset diabetes of the young, and Neonatal diabetes

Table 2 Different types of the most common monogenic diabetes and their characteristics

Phenotypes	Responsible gene	Characteristics
HNF1A-MODY	HNF1A	Loss of function of the β-cell transcription factor, glucosuria,
GCK-MODY	GCK	Reduced glucokinase enzyme function, raising insulin secretion setpoint
HNF1B-MODY	HNF1B	Pancreatic/renal transcription factors' loss of functioning, genitourinary/renal malformations, exocrine pancreatic insufficiency, hypomagnesemia, variations in liver function tests, developmental delay, hyperuricemia
KCNJ11-NDM	KCNJ11	Mutation in the β-cell KATP channels' Kir6.2 subunit leads to impaired neuro-developmental dysfunction of insulin secretion
ABCC8-MODY	ABCC8	Mutation in the β-cell KATP channels' SUR1 subunit, leading to impaired insulin secretion and neurodevelopmental dysfunctions
INS-NDM and-MODY	INS	abnormalities in the proinsulin gene leading to a gradual deterioration of β-cell functioning capability due to the accumulation of improperly coiled proinsulin proteins

KATP: ATP-sensitive potassium; NDM: Neonatal diabetes mellitus; MODY: Mature-onset diabetes of the young; INS: Insulin gene; HNF1A: Hepatic nuclear factor 1α; GCK: Glucokinase; HNF1B: Hepatic nuclear factor 1b.