Endocrine Abstracts

Introduction: MODY 5 is a rare type of dominantly inherited diabetes mellitus. It is asociated with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene. They are mostly missense mutations that produce truncated proteins with a variable clinical spectrum that encompasses among others: kidney, genital and pancreatic abnormalities.

Case-report: A 35 years-old man without relevant medical history, presented with acute hypergycemia (541 mg/dl) and ketosis but wihout metabolic acidosis. He had had cardinal symptoms for a 2-week period before presentation. Further investigation revealed a diagnosis of early onset diabetes in his mother, three siblings and a niece who also had undergone nephrectomy due to polycystic kydney disease. Laboratory workout revealed acute renal injury (MDRD4 57.2 ml/min per 1.73 m²) and elevated liver enzymes with a cholestatic pattern (Gamma-GT 74U/l; Alkaline Phosphatase 154 U/l; Bilirrubin 1.7 mg/dl), both resolved before discharge. No other abnormalities were detected. Abdominal US was normal. During hospitalization, the patient progressively achived adecuate glucose and he was discharged with a basal-bolus insulin regimen, pending on the results of pancreatic autoimmunity, and the performance of a magnetic cholangioresonance. During follow-up the patient showed no evidence of islet-cell antibodies nor glutamic acid decarboxylase autoantibodies (Anti GAD65 0.46 IU/ml, Anti IA2 2.13 U/ml, anti insulin 0.51 U/ml), a C- peptide of 237 ng/ml and the magnetic cholangioresonance that revealed aplasia of the dorsal pancreas. The diagnosis of MODY 5 diabetes was made after a genetic study for detecting HNF-1beta gene mutations confirmed a missense mutation (M_000458.2:c.884G>A -p.Arg295His-) in the DNA-binding homeodomain. The insulin was progressively withdrawn and metformin was introduced.

Conclusion: MODY 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-1B is warranted in young patients with an AD pattern family history of diabetes particularly when pancreatic atrophy, kidney or genital abnormalities are present.