Congenital hyperinsulinism is a rare but significant cause of severe and persistent hypoglycaemia in infancy. Although a biphasic phenotype of congenital hyperinsulinism in infancy followed by Maturity-Onset Diabetes of the Young (MODY) in later life has been established for HNF4A, the existence of a similar phenotype for a related MODY gene, HNF1A, is less clear. We describe two cases of congenital hyperinsulinism in association with dominantly inherited variants in HNF1A. They presented in the early neonatal period with unequivocal biochemical evidence of congenital hyperinsulinism and persistence into childhood with ongoing need for medical therapy. Both cases inherited HNF1A variants from a parent with a diabetes phenotype consistent with MODY, without obesity, insulin resistance or other metabolic syndrome features. In the first case, a paternally inherited novel c.-230_-101del variant was found that deletes the minimal promoter region presumably required for HNF1A expression. In the second case, a maternally inherited missense variant (c.713G>T, p.(Arg238Met)) was identified. This variant is predicted to cause haploinsufficiency via aberrant splicing and has previously been associated with MODY but not congenital hyperinsulinism. Our cases further strengthen the evidence for HNF1A as a CHI-causing gene requiring long-term follow-up.

先天性高胰岛素血症是婴儿严重和持续性低血糖的罕见但重要原因。虽然已经为HNF4A建立了婴儿期先天性高胰岛素血症的双相表型，然后在以后的生活中出现了年轻的成年糖尿病（MODY），但是对于相关的MODY基因HNF1A的相似表型的存在还不清楚。我们描述了与HNF1A的显性遗传变异相关的先天性高胰岛素血症的两个案例。他们在新生儿早期就提供了明确的生化证据，证明先天性高胰岛素血症和持续存在于儿童中并持续需要药物治疗。两种情况都继承了HNF1A糖尿病表型与MODY一致的父母亲的变体，没有肥胖，胰岛素抵抗或其他代谢综合征的特征。在第一种情况下，发现了父本遗传的新颖c.-230_-101del变体，该变体删除了可能为HNF1A表达所需的最小启动子区域。在第二种情况下，鉴定出母系遗传的错义变体（c.713G> T，p。（Arg238Met））。预计该变异体会通过异常剪接导致单倍体功能不足，并且先前已与MODY相关，但与先天性高胰岛素血症无关。我们的病例进一步加强了将HNF1A作为引起CHI的基因的证据，需要长期随访。