ESPE Abstracts

Background: Hepatocyte nuclear factor 1β (HNF1β) is a critical transcription factor that regulates the development of the kidneys, pancreas, liver and genital tract. Patients with deletions and mutations in the HNF1 β gene present with renal and extrarenal manifestations. The most important extrarenal finding is diabetes, also known as MODY5. Although it is generally diagnosed with hyperglycemia, diabetic ketoacidosis is rarely seen.

Case: A fifteen-year-old male patient was admitted with diabetic ketoacidosis with polyuria, polydipsia, and weight loss for 1 month. History revealed that the patient was diagnosed with antenatal hydronephrosis and nonatal hyperglycemia on the postnatal 2nd day resolving in two days. There was no consanguinity in the family history of the patient who underwent right pyeloplasty at the age of 6 months. There were individuals diagnosed with DM at an advanced age on the paternal side of the patient. On physical examination, height was 174 cm (+0.33 sds), weight was 94.5 kg (+2.32 sds), and BMI: 31.2 (+2.32 sds), pubertal stage was Tanner 4.

Laboratory Results: pH: 7.13, HbA1c: 13.6%, c-peptide: 0.53 ng/mL, glucose: 592 mg/dl. Aanti-GAD, ICA, IAA antibodis were negative MODY5 was considered based on diabetes and the history of hydronephrosis, asymptomatic elevation of transaminases and hypomagnesemia. Ultrasound examination revealed multicystic kidney. Genetic analysis showed c.957_966del (p.Ser319Argfs*) heterozygous mutation in HNF1β gene confirming the diagnosis of MODY5. Pancreatic dorsal agenesis was also detected in the MRI of the patient. Additionally, MC4R gene, which was examined in the CES panel due to obesity revealed c.821A>G p.(Asn274Ser) missense mutasyon in Exon1. The patient was started on insulin tretment 1.5 U/kg/g which was discontinued during follow-up and the final HbA1c value was 5.9%.

Results: Since obesity is common nowadays (whether it is due to a genetic cause or not), it should be kept in mind that individuals with MODY may also be obese, and it should not be directly associated with Type 2 DM. In addition, although DKA is typically seen in Type 1 DM, MODY should be considered in the differential diagnosis in the presence of atypical findings such as a history of renal disease and antibody negativity.