title: Hyperinsulinism in tyrosinaemia type I.
abstract: Tyrosinaemia type I (TT I) (McKusick 276700) is a heterogeneous disorder with a broad spectrum of clinical phenotypes. Although histological abnormalities of the pancreas are well recognized, there are only incidental reports of pancreatic dysfunction manifested as insulin-dependent diabetes mellitus. We report three subjects with TT I and acute liver dysfunction who had hyperinsulinism in early infancy. Hypoglycaemia persisted despite dietary treatment and one patient had inadequate lipolysis at the time of hypoglycaemia. All three patients were successfully treated with diazoxide (10 mg/kg per day) and chlorthiazide (35 mg/kg per day) and treatment was gradually withdrawn after 9, 13 and 34 months, respectively. The mechanism of pancreatic dysfunction in TT I is unknown but may be related to the toxic metabolites that accumulate in this condition. We conclude that hyperinsulinism is not a rare complication in TT I. In patients with persistent hypoglycaemia, C-peptide should always be measured. Treatment with diazoxide and chlorthiazide is highly effective, appears to be safe, and does not need to be continued lifelong.
authors.affiliation: The Liver Unit, Birmingham Children's Hospital, Birmingham, UK. Ulrich.Baumann@bch.nhs.uk
authors.forename: U
authors.initials: U
authors.lastname: Baumann
authors.forename: M A
authors.initials: MA
authors.lastname: Preece
authors.forename: A
authors.initials: A
authors.lastname: Green
authors.forename: D A
authors.initials: DA
authors.lastname: Kelly
authors.forename: P J
authors.initials: PJ
authors.lastname: McKiernan
mesh_terms: D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D002740:Chlorothiazide / Q000627:therapeutic use; D003981:Diazoxide / Q000627:therapeutic use; D004232:Diuretics; D006801:Humans; D006946:Hyperinsulinism / Q000175:diagnosis* / Q000209:etiology*; D007003:Hypoglycemia / Q000175:diagnosis / Q000209:etiology; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D008107:Liver Diseases / Q000175:diagnosis / Q000209:etiology; D010182:Pancreatic Diseases / Q000175:diagnosis / Q000209:etiology; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use; D020176:Tyrosinemias / Q000150:complications* / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004232:Diuretics; D007328:Insulin; D049993:Sodium Chloride Symporter Inhibitors; D002740:Chlorothiazide; D003981:Diazoxide