A Japanese school urine screening program led to the diagnosis of KCNJ11-MODY: A case report
Akito Hattori1, Koji Okuhara1, Yasuhiro Shimizu1
1Department of Pediatrics, Tenshi Hospital, Hokkaido, Japan.
Insights
Maturity-onset diabetes in the young (MODY) due to KCNJ11 mutations is rare. This case highlights a novel KCNJ11 variant in a Japanese girl, successfully treated with low-dose sulfonylurea, emphasizing genetic testing for early diagnosis.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Neonatal diabetes mellitus is primarily caused by KCNJ11 mutations.
- Maturity-onset diabetes in the young (MODY) linked to KCNJ11 mutations is infrequently reported.
- Early identification and genetic analysis are crucial for diagnosing diabetes subtypes.
Observation:
- A 12-year-old Japanese female presented with hyperglycemia detected via school urine screening.
- Impaired insulin secretion was observed, with no islet autoantibodies detected.
- Genetic analysis identified a novel heterozygous KCNJ11 variant (c.153G>C, p.Glu51Asp).
Findings:
- The patient's father shared the same KCNJ11 mutation and was diagnosed with diabetes at 46.
- The identified KCNJ11 variant was classified as likely pathogenic according to ACMG guidelines.
- Sulfonylurea treatment, specifically glibenclamide at 0.02-0.03 mg/kg/d, achieved adequate glycemic control.
Implications:
- This case expands the known spectrum of KCNJ11-related diabetes.
- Low-dose sulfonylurea therapy is effective for this specific KCNJ11 mutation.
- Genetic testing for KCNJ11 and other causative genes is recommended for school-aged patients with diabetes.
Abstract:
Although KCNJ11 mutation is the main cause of neonatal diabetes mellitus, reports of maturity-onset diabetes in the young (MODY) related to KCNJ11 are rare. Here, we report a case of KCNJ11-MODY in a 12-yr-old Japanese female. Hyperglycemia was initially detected during a school urine screening program. Subsequent laboratory examinations revealed impaired insulin secretion; however, no islet autoantibodies were detected. Genetic testing of KCNJ11 revealed a novel heterozygous variant, c.153G>C, p.Glu51Asp. The patient's father had the same mutation and was diagnosed with diabetes at 46 yr of age. KCNJ11-MODY was suspected, and sulfonylurea administration resulted in adequate glycemic control in the patient. The American College of Medical Genetics and Genomics guidelines classify this variant as likely pathogenic, and the effectiveness of sulfonylureas supports its pathogenicity. The patient could be treated with 0.02-0.03 mg/kg/d of glibenclamide, as this mutation may be responsive to only a small amount of sulfonylurea. A detailed family history and sequencing of causative genes, including KCNJ11, may help diagnose diabetes in school-aged patients.
