Hepatocyte Nuclear Factor-4 Alfa Mutation Associated with Hyperinsulinaemic Hypoglycaemia and Atypical Renal Fanconi Syndrome: Expanding the Clinical Phenotype

Horm Res Paediatr. 2016;86(5):337-341. doi: 10.1159/000446396. Epub 2016 Jun 1.

Abstract

Background: The p.R63W mutation in the hepatocyte nuclear factor-4 alpha (HNF4A) results in macrosomia and atypical Fanconi syndrome, in addition to hyperinsulinaemic hypoglycaemia (HI). We describe 2 infants carrying this mutation, presenting with additional features. Cases Series: Patient 1, a male born with a birth weight of 1.7 SDS, was diagnosed with HI on day 2 of life. He responded to 3-10 mg/kg/day of diazoxide. Raised serum creatinine led to the investigation of renal tubular function, showing leaking of electrolytes and protein. The patient also had conjugated hyperbilirubinaemia with liver steatosis. Patient 2 was a male born with a weight of 0.36 SDS. His mother had renal Fanconi syndrome. He received parenteral nutrition and presented with HI at 1 month of age, while establishing enteral feeds. Biochemistry workup showed renal tubular leaking of calcium, sodium, and phosphate. A hypoglycaemia screen documented HI, and the patient was commenced on 2 mg/kg/day of diazoxide. Continuous glucose monitoring was performed in his mother, revealing overnight hypoglycaemia.

Conclusion: Renal Fanconi syndrome represents the only HNF4A feature showing complete penetrance. Our cases suggest that the p.R63W HNF4A mutation must be considered in subjects with a normal birth weight and postulate the possibility of liver involvement as a part of this condition.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Blood Glucose / metabolism
  • Congenital Hyperinsulinism / blood
  • Congenital Hyperinsulinism / drug therapy
  • Congenital Hyperinsulinism / genetics*
  • Diazoxide / administration & dosage
  • Fanconi Syndrome / blood
  • Fanconi Syndrome / drug therapy
  • Fanconi Syndrome / genetics*
  • Hepatocyte Nuclear Factor 4 / genetics*
  • Humans
  • Infant, Newborn
  • Male
  • Mutation, Missense*

Substances

  • Blood Glucose
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Diazoxide