Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4α (HNF4A)

Excerpt

To the Editor: In a recent publication, Pearson et al. [1] reported on a previously unrecognised feature of the natural history of the type 1 form of maturity onset diabetes of the young (MODY1), which is caused by mutations in the gene encoding hepatocyte nuclear factor 4α (HNF4A). In a comparison of 54 mutation carriers (from 15 European pedigrees and with 12 different mutations) with their unaffected family members, they found a significant increase in median birthweight (790 g) with a 56% prevalence of macrosomia compared with 13% in family members without mutations. Macrosomia was inherited from either mother or father (64 and 46% of total cases, respectively). Transient neonatal hypoglycaemia was reported in eight of 54 neonates, three of whom had documented hyperinsulinaemia as infants. Similar observations were made in a mouse model with a beta cell-specific Hnf4a deletion [1]. …