De novo mutation in HNF-1β gene as a cause for Maturity-onset Diabetes of the Young type 5 with sustained hypomagnesemia

Maturity-onset Diabetes of the Young type 5 (MODY5) is clinically heterogeneous, and the genetic examination is important to provide the accurate diagnosis. Identification of more cases will better understand the genotype-phenotype correlations of this disorder. We collected the clinical and biochemical data, using the whole-exome gene detection and multiplex ligation–dependent probe Amplification to detect the pathogenic gene variants. The proband is a 39-year-old female, and presenting with symptoms including polyuria, polydipsia, and weight loss for 6 months. Her BMI was 17.6 kg/m2. Laboratory tests indicated hypokalemia (3.1 mmol/L), hypomagnesemia (0.4 mmol/L), and hypocalcemia (1.91 mmol/L). Glycated hemoglobin (HbA1c) was 13.7%, fasting C-peptide was 0.24 ng/mL (normal range: 0.3–3.73 ng/mL). Both glutamic acid decarboxylase and islet cell antibodies were negative. Abdominal magnetic resonance image showed the agenesis of the tail and body of the pancreas and the presence of disseminated cysts of the left kidney. Genetic examination displayed a de novo heterozygous deletion of the whole HNF-1Β gene (NM_000458.3). Three-year follow-up after the diagnosis showed that the patient has sustained hypomagnesemia and cannot maintain an appreciable increase in serum magnesium levels (0.52–0.61 mmol/L), although she was using the double-dose magnesium aspartate. Moreover, she cannot achieve good glucose control either. Our findings indicted that MODY is highly heterogeneous and patients with additional extrapancreatic clinical features and hypomagnesemia should be screened for MODY5.