1. Hepatocyte Nuclear Factor-4 Alfa Mutation Associated with Hyperinsulinaemic Hypoglycaemia and Atypical Renal Fanconi Syndrome: Expanding the Clinical Phenotype.
- Author
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Improda N, Shah P, Güemes M, Gilbert C, Morgan K, Sebire N, Bockenhauer D, and Hussain K
- Subjects
- Amino Acid Substitution, Blood Glucose metabolism, Congenital Hyperinsulinism blood, Congenital Hyperinsulinism drug therapy, Diazoxide administration & dosage, Fanconi Syndrome blood, Fanconi Syndrome drug therapy, Humans, Infant, Newborn, Male, Congenital Hyperinsulinism genetics, Fanconi Syndrome genetics, Hepatocyte Nuclear Factor 4 genetics, Mutation, Missense
- 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., (© 2016 S. Karger AG, Basel.)
- Published
- 2016
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