RFX6 heterozygous frame-shift variation causes maturity-onset diabetes mellitus of the young (MODY) with refractory hyperlipidemia: a case report

Abstract

Background: Maturity-onset diabetes mellitus of the young (MODY) is a form of autosomal dominant inherited diabetes, featuring diverse clinical characteristics due to distinct pathogenic gene mutation sites. Reports on MODY caused by RFX6 mutations are scarce, and it is prone to being misdiagnosed as type 1 or type 2 diabetes in clinical settings. To date, no cases have been reported regarding patients with RFX6 gene mutations accompanied by refractory hyperlipidemia, and the treatment remains undetermined. We present a rare case of a 13-year-old Chinese girl who was admitted to the Third Affiliated Hospital of Soochow University with diabetes combined with refractory hyperlipidemia.

Case description: A 13-year-old adolescent female presented with persistent dry mouth, polydipsia, and polyuria. The physical examination accidentally found high blood glucose. She had refractory hyperlipidemia in the past and was treated with a variety of lipid-lowering programs, but her lipids were still poorly controlled. Due to the patient's early age of onset, the special type of diabetes cannot be excluded, and she is recommended to be further examined in our hospital.

Conclusions: We sequenced the MODY-related genes of the patient and her mother. RFX6 heterozygous frame-shifting variants were found in the proband and her mother (NNM_173560:c.1500delT). The patient was eventually diagnosed with MODY. During the hospitalization, we treated the patient with insulin hypoglycemic treatment, and the patient's blood glucose was stable. Surprisingly, the patient's blood lipid also decreased significantly, and even without using any lipid-lowering drugs, the blood lipid remained at a low level.

Keywords: Maturity-onset diabetes mellitus of the young (MODY); RFX6; case report; hyperlipidemia.

Figure 1

Blood lipid administration and control curve. (A) Pitavastatin 2 mg once daily + ezetimibe 10 mg once nightly + fenofibrate 0.2 g once daily; (B) fenofibrate 0.2 g once daily + evolocumab injection 140 mg once weekly. The black arrow indicates the date of admission. The black curve represents the patient’s TC trend, the red curve shows TG levels, the dark blue curve depicts HDL changes, and the purple curve illustrates LDL variations. HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total cholesterol; TG, triglyceride.