title: Hepatocyte Nuclear Factor-4 Alfa Mutation Associated with Hyperinsulinaemic Hypoglycaemia and Atypical Renal Fanconi Syndrome: Expanding the Clinical Phenotype.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Improda
authors.forename: Pratik
authors.initials: P
authors.lastname: Shah
authors.forename: Maria
authors.initials: M
authors.lastname: Güemes
authors.forename: Clare
authors.initials: C
authors.lastname: Gilbert
authors.forename: Kate
authors.initials: K
authors.lastname: Morgan
authors.forename: Neil
authors.initials: N
authors.lastname: Sebire
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000378:metabolism; D044903:Congenital Hyperinsulinism / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D003981:Diazoxide / Q000008:administration & dosage; D005198:Fanconi Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense
chemical_list: D001786:Blood Glucose; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D003981:Diazoxide