Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

A Diabeto‘genic’ Syndrome: HNF1B mutation and a severe case of anuric renal failure causing perinatal mortality (#340)

Wenlin Cecilia Chi 1 , Jenny Gunton 1 2
  1. Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia
  2. University of Sydney, Sydney, NSW, Australia

Introduction: Hepatocyte Nuclear Factor 1b (HNF1b) mutation causes Maturity Onset Diabetes of the Young type 5 (MODY 5). Classically, patients present with early onset diabetes, and may have renal and genitourinary abnormalities. We report the first case of anuric renal failure in an infant with HNF1b mutation.

Case: A 29 year old lady presented with overt diabetes (GTT 2 hour BGL >18.5mmol/l) diagnosed at 26 weeks gestation. HbA1c was 6.8%, and Islet cell and GAD antibodies were negative. Fetal morphology scan showed enlarged kidneys with multiple cysts, and no bladder was visualised.

A live female infant was delivered at 32 weeks. Ultrasound showed bilateral dysplastic kidneys with no detectable urinary bladder or collecting system. She died from anuric renal failure at eight days of life. Genetic testing showed a heterozygous chromosome 17q12 deletion, including deletion of HNF1b.

Genetic testing on both parents showed that the mother had the same heterozygous deletion. Of note, her renal ultrasound was normal and her only renal manifestation was hypomagnesaemia (Mg 0.35mmol/l) due to increased renal loss.

Discussion: It is not uncommon for patients with MODY to be diagnosed during pregnancy. MODY 5 is increasingly recognised to cause a spectrum of manifestations affecting the kidneys, pancreas, genitourinary tract, and liver. These manifestations vary in severity and we present a case of severe renal involvement causing anuric renal failure. Genetic testing can potentially provide a diagnosis both antenatally or pre-conception. However, unclear genotype phenotype correlation creates difficulty in decision making.

Conclusion: Although MODY 5 is a rare cause of diabetes, the diagnosis may have severe implications for babies. It is therefore important to consider screening for the mutation in pregnant women with unusual presentations of diabetes during pregnancy, especially if there are associated fetal or maternal renal or genitourinary abnormalities, or maternal hypomagnesaemia.