Supplementary Material for: An unusual liver and kidney involvement in congenital hyperinsulinism with HNF1A mutation: a case report

Background Hepatocyte nuclear factor-1α (HNF-1α) and hepatocyte nuclear factor-4α (HNF-4α) are transcription factors highly expressed in β-cells, hepatocytes, intestinal epithelial cells, and renal tubular cells. Variants in both genes have been linked to maturity-onset diabetes of youth (MODY) and congenital hyperinsulinism (HI). To date, the association between HI, renal tubulopathy and hepatopathy has been described only in patients with HNF-4α deficiency. HI due to HNF-1α deficiency has not been linked to extra-pancreatic features. Case description Our patient presented neonatal onset of HI and hepatomegaly, cholestasis, echographic features of liver steatosis and renal tubulopathy (glycosuria, phosphaturia, aminoaciduria, uricuria, proteinuria) from the first month of life. The molecular analysis revealed a heterozygous maternal variant c.4432G>A (p.Gly1478Ar) in the ABCC8 gene and a heterozygous maternal variant c.1859C>T (Thr620Ile) in HNF1A gene. We describe an 8-month follow-up and discuss possible pathogenetic mechanisms linking HNF1A-HI and features of extrapancreatic involvement. Conclusions Our case describes a likely association between HI due to HNF-1α deficiency with liver and kidney involvement. Further cases are needed to validate our hypothesis and to establish if a genotype-phenotype correlation exists in case of extra-pancreatic involvement, as for the known HNF4A mutation-specific phenotype.