Endocrine Abstracts

Introduction

Maturity Onset Diabetes of the Young (MODY) affects 1–2% of diabetic patients. Subtype 5 (HNF1β mutation) is rare (~1% of all MODY subtypes) and extra-pancreatic manifestations are often present (chronic kidney disease (CKD), liver disease and/or genitourinary malformations).

Aim

To report and review confirmed MODY 5 cases in an Endocrinology Department.

Methods

Retrospective study of patients with HNF1β mutation followed between 2013 and 2020.

Results

We found 10 patients (6 female) with HNF1β mutation (7 index cases). The median age at MODY 5 diagnosis was 40.5 (IQR 35–58) years old. Six patients were first classified as having type 1 diabetes and 4 as type 2. Diabetes was the first manifestation of MODY 5 in 50% of cases. The median age of diabetes diagnosis was 28 (IQR 16–40) years old. The average time between diabetes and MODY 5 diagnosis was 16.5 years old. Insulin therapy was prescribed in 8 patients (started at diabetes diagnosis in 75% of cases). The average diabetes evolution time was 19.4 years old. In 50% of the cases CKD in pediatric age was the first manifestation of MODY 5. These patients not only had progressive renal failure but also renal malformations: unilateral kidney hypoplasia (n = 1), bilateral kidney hypoplasia (n = 1) and solitary kidney (n = 1). Two patients were submitted to kidney, one to combined kidney and pancreas, and one to combined kidney and liver transplantations. All patients have functioning kidney graft. CKD was present in 7 patients. Additional long-term complications of diabetes include retinopathy (n = 3), peripheral neuropathy (n = 1) and ischemic cardiomyopathy (n = 1). Regarding other extra-pancreatic manifestations: cholestatic liver disease (n = 4) and genital malformation (bicornuate uterus) (n = 1). History of a first-degree relative with diabetes and/or nephropathy diagnosed at a young age was present in 71.4% (n = 5) of the index-cases.

Conclusions

Despite being a rare disease, MODY 5 is underdiagnosed and often classified as another type of diabetes. It should be considered in patients with diabetes and CKD especially at a young age, if family history is suggestive and nephropathy appears before/shortly after the diagnosis of diabetes. Presence of liver disease increases the degree of suspicion. Early diagnosis allows the risk of complications to be minimized and to carry out pre-conception genetic counseling.