Childhood-onset mild diabetes caused by a homozygous novel variant in the glucokinase gene

• Published in: Hormones (Athens, Greece) Vol. 21; no. 1; pp. 163 - 169
• Main Authors: Filibeli, Berna Eroğlu, Çatli, Gönül, Ayranci, İlkay, Manyas, Hayrullah, Kirbiyik, Özgür, Dündar, Bumin
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-03-2022
• Subjects: Adolescent; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - genetics; Endocrinology; Glucokinase - genetics; Homozygote; Humans; Hyperglycemia; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Mutation; Phenotype; Teaching Case Presentations; Heterozygous mutation; GCK-MODY; Permanent neonatal diabetes; gene; Glucokinase; Homozygous mutation; Glucokinase (GCK) gene
• ISSN: 1109-3099; 2520-8721
• DOI: 10.1007/s42000-021-00330-1

Purpose
Heterozygous loss-of-function mutations in the glucokinase (
GCK
) gene cause MODY 2, which is characterized by asymptomatic fasting hyperglycemia and does not require insulin treatment. Conversely, homozygous loss-of-function mutations in the same gene give rise to permanent neonatal diabetes mellitus (DM) that appears in the first 6–9 months of life and necessitates lifelong insulin treatment. We aimed to present the genotypic and phenotypic features of a 13-year-old patient diagnosed with DM at the age of 3 years due to a homozygous variant in the
GCK
gene
.
Methods
The patient’s clinical and laboratory findings at follow-up were not consistent with the initial diagnosis of type 1 DM; thus, next-generation sequencing of MODY genes (
GCK
,
HNF1A
,
HNF1B
, and
HNF4A
genes) was performed to identify monogenic causes of DM.
Results
A novel homozygous variant c.1222 G > T in the
GCK
gene was revealed. In silico analysis identified it as a pathogenic variant. His mother, father, and brother had the same heterozygous variant in the
GCK
gene and were diagnosed with MODY 2 (mild fasting hyperglycemia and elevated HbA1c) after genetic counseling.
Conclusion
In this case report, a patient with a homozygous variant in the
GCK
gene, who was diagnosed with DM after the infantile period, was presented, highlighting the fact that cases with homozygous variants in the
GCK
gene can, though rarely, present at a later age with a milder phenotype.