Prenatal diagnosis of HNF1b mutation allows recognition of neonatal dysglycemia

Fernanda Iafusco,Dario Iafusco,Serena Meola,Carmine Pecoraro,Nadia Tinto,Cristina Mazzaccara

doi:10.1007/s00592-020-01641-2

Abstract

Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes in Europe, affecting between 1 and 6% of diabetic patients. It comprises a group of heterogeneous genetic disorders characterized by early onset of diabetes (commonly before age 25), absence of autoimmunity, and beta-cell dysfunction. So far, mutations in 14 different genes involved in glucose homeostasis and pancreatic development [1] have been associated with this disease. Although it is an autosomal dominant disorder, de novo mutations should be taken into consideration in patients without a family history of diabetes. Most cases of MODY are due to mutations in GCK, HNF1a, HNF4a and HNF1b, previously known as MODY2, MODY3, MODY1, and MODY5, respectively. Among these, HNF1b is an active transcription factor that forms homodimers or heterodimers with HNF1a and plays a fundamental role in kidney development, nephron differentiation, and pancreatic growth and differentiation. Mutations in this gene lead to congenital anomalies of the kidney and urinary tract, genital malformations, pancreatic atrophy with endocrine and exocrine deficiency [2]. Diabetes usually onsets in early adulthood and frequently requires insulin treatment. We present an unusual case of a prenatal diagnosis that revealed a mutation in the HNF1b gene responsible for neonatal hyperglycemia in a pregnant woman affected by X-linked ectodermal dysplasia.

Highlights

Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes in Europe, affecting between 1 and 6% of diabetic patients
Mutations in the HNF1b gene are responsible for the development of HNF1b/MODY, which is associated with distinctive clinical features, including pancreatic atrophy and renal disease [2, 3]
This case underlines that newborns carrying HNF1b mutations must be constantly and carefully monitored over time even if born to normo-glycemic mothers to possibly detect the early signs of diabetes

Summary

Introduction

Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes in Europe, affecting between 1 and 6% of diabetic patients. Mutations in 14 different genes involved in glucose homeostasis and pancreatic development [1] have been associated with this disease. It is an autosomal dominant disorder, de novo mutations should be taken into consideration in patients without a family history of diabetes. Blood glucose levels ranged from 80 to 150 mg/dL (4.44–8.33 mmol/L) during most of the monitoring time, whereas they were below 70 mg/dL (3.89 mmol/L) and above 150 mg/dL (8.33 mmol/L) for short periods of time Based on these test results, we diagnosed a "neonatal form of HNF1b dysglycemia”

Discussion

Conclusion

Findings

Compliance with ethical standards