This report describes GCK-MODY in a Chinese family and stresses that in managing this condition it is important to avoid unnecessary drug treatment and excessive anxiety about mild hyperglycemia.
At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA<sub>1c</sub> <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY.
However, recent analyses have also demonstrated ABCC8 gene mutations in patients with monogenic diabetes (maturity onset diabetes of the young, MODY), with milder clinical phenotypes and later onset of hyperglycemia.
This case raises the question as to whether hyperglycaemia in GCK-MODY may increase the risk of fetal caudal regression syndrome as reported in women with pre-existing diabetes mellitus.
We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes.
Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children's hospital in South China.
The findings leading to the diagnosis were impaired fasting glucose (IFG) (15/37), symptoms of hyperglycemia (4/37), and a GCK-MODY family history (18/37).
People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4-8.3 mmol/L, HbA1c range 5.8-7.6% [40-60 mmol/mol]), which is present from birth and shows slight deterioration with age.
However, mutations in the HNF1A and HNF4A cause a progressive pancreatic β-cell dysfunction and hyperglycemia that can result in microvascular complications.
Out of these 78 people with GCK-MODY and 40 additional family members with hyperglycaemia whose genetic status was unknown, only one had diabetic nephropathy.
Family history for mild hyperglycaemia and GADA fluctuation alerted us to a possible MODY diagnosis which was confirmed by detection of GCK mutation c.626C>T; p.T209M.
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.
In contrast, mutations in the genes encoding the transcription factors HNF1A and HNF4A cause a progressive insulin secretory defect and hyperglycaemia that can lead to vascular complications.
MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation and early need of insulin therapy to control hyperglycemia).
We genetically analyzed four families of young children with fasting hyperglycemia with family histories of diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha (HNF4alpha), glucokinase (GCK), and hepatocyte nuclear factor 1 alpha (HNF1alpha), the genes responsible for MODY1, MODY2, and MODY3, respectively.
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young.