A Rare Case of MODY12 Complicated with Gitelman Syndrome: A Case Report and Literature Review

Jinlan Xie, Yuan Li, Qingqing Ma, Feifei Zhong and Juhong Yang*

Department of Endocrinology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Zhanjiang, China People's Hospital of Dongxihu District, Wuhan, China

^*Correspondance to: Juhong Yang 

 PDF  Full Text Case Report | Open Access

Abstract:

Background: Maturity-onset diabetes of the young type 12 (MODY12) and Gitelman syndrome are both classified as rare diseases. Gitelman syndrome increases the risk of type 2 diabetes by contributing to hypokalemia, hypomagnesemia and hyperaldosteronemia, all of which disrupt insulin secretion and lead to insulin resistance. Nevertheless, other types of diabetes are rarely associated with Gitelman syndrome. This report presents an uncommon case of MODY12 cooccurring with Gitelman syndrome, associated with a novel mutation in the ABCC8 gene. Case Summary: A 21-year-old male patient was admitted to our hospital with the symptoms of polyuria and polydipsia for 3 months. Laboratory tests revealed a fasting plasma glucose (FPG) of 13.7 mmol/L, a 2-hour postprandial glucose level of 24.2 mmol/L, and a glycosylated hemoglobin (HbA1c) of 13.6%. The patient demonstrated impaired insulin secretion (fasting C peptide: 0.37 nmol/L; 2 hours oral glucose tolerance test (OGTT) C peptide: 0.85 nmol/L). Additionally, the patient presented with hypokalemia (2.62 mmol/L), hypomagnesia (0.35 mmol/L), metabolic alkalosis (pH 7.439, HCO3- 33.3 mmol/L) and hyperaldosteronism (renin 66.52 ng/mL/h; aldosterone 942.228 pg/mL), while blood pressure remained within normal limits (99/77 mmHg). Furthermore, genetic analysis through next-generation sequencing (NGS) identified a missense variant in the ABCC8 gene (NM_00352.4: c.892C>T; NM_005544.2: c.1435C>T) and the IRS1 gene (/NM_005544.2: c.1435C>T). The patient received a diagnosis of MODY12 co-occurring with Gitelman syndrome. Genetic evaluation revealed a paternal heterozygous carrier status for the ABCC8 gene mutation. Sulfonylurea therapy resulted in better glycemic control. Potassium homeostasis was achieved through daily supplementation with 6.0 g of potassium chloride sustained-release tablets (262 mg/tablet). Conclusion: This case report presents a rare co-occurrence of MODY12 and Gitelman syndrome with a novel stop-gain mutation in the ABCC8 gene. Although no correlation was found between the ABCC8 gene mutation and Gitelman syndrome in this case, the possibility of Gitelman syndrome should be evaluated in MODY12 patients exhibiting hypokalemia, hypomagnesemia, hypochloremia, metabolic alkalosis, elevated renin and aldosterone levels, and normotension.

Keywords:

Diabetes, MODY12, Gitelman syndrome, ABCC8, IRS1

Cite the Article:

Xie J, Li Y, Ma Q, Zhong F, Yang J. A Rare Case of MODY12 Complicated with Gitelman Syndrome: A Case Report and Literature Review. Ann Clin Case Rep. 2025; 10: 2777..