Endocrine Abstracts

Introduction: MODY 5 is a rare form of autosomal dominant monogenic diabetes with a broad phenotypical spectrum that occurs with pancreatic and extra-pancreatic clinical manifestations, such as: malformation and dysfunction of the pancreas, nephrourologic anomalies, impaired renal function, hepatopathy and neurocognitive defects. It is caused by a mutation of the gene encoding hepatocyte nuclear transcription factor 1 beta (HNF1β).

Case 1: Male, 8 years-old with a history of developmental delay, facial dysmorphia, macrocephaly and pielic dilatation. At the age of three a genetic test revealed 17q12 microdeletion associated with HNF1β mutation. Blood analysis revealed a HbA1c: 5,4% and C-peptide (C.pep): 1.09ng/ml (RR: 1.1-4.4). To date, at the age of eight, he remains euglycemic, with a HbA1c 5,5% and a C.pep 0,94 ng/ml, without any treatment.

Case 2: Male, 15 years-old, diagnosed with renal cysts and motor skills disorder. At age of 14 a genetic test revealed 17q12 deletion. To this date the patient remains euglycemic, with a HbA1c: 5,2%, without any treatment.

Case 3: Female, died at 49 years of age with sepsis, with a history of developmental delay, diabetes diagnosed at 16 years of age, kidney chronic disease and hepatopathy of unknown etiology. Started hemodialysis at the age of 43, renal transplant at 46 years-old. Genetic test revealed a 17q12 deletion associated with HNF1β mutation. She was on insulin therapy.

Case 4: Male, 16 years-old, diagnosed with CKD G2A2 KDIGO, multiple bilateral renal cysts and pielic dilatation. At age of six, a diagnosis of diabetes was made (insulin deficiency symptoms and no acute complications) and started insulin. Abdominal CT scan revealed pancreatic agenesis. C.pep <0.02 ng/ml. Genetic test revealed: HNF1β - c.301G>T(p.E101*). Currently the patient is on functional insulin therapy. HbA1c: 7.2%.

Case 5: Male, 23 years-old with progressive renal dysfunction due to bilateral renal cysts, underwent kidney transplant at the age of 19. After a few weeks diabetes was diagnosed (HbA1c 8% and C.pep. 3.89 ng/ml) and started on insulin. Genetic test revealed: HNF1β – variant c.443C>T (p.S148L). Last visit: HbA1c 8,3%, C.pep. 4.06 ng/ml, Cr: 2.5 mg/dl and GFR: 36 ml/min/1.73 m².

Conclusion: HNF1β gene mutation phenotype is variable and there are no pathognomonic manifestations, nevertheless, it should be suspected in patients with unusual diabetes and multisystem involvement unrelated to diabetes, especially, renal disease. Diabetes in these mutations can develop at any age. Neurodevelopmental disorders, diabetes, nephrourologic anomalies and hepatic abnormalities may raise suspicion of a 17q12 deletion syndrome.