title: [Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].
abstract: Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory.
authors.affiliation: Servicio de Pediatría y Unidad de Endocrinología Pediátrica, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, España; Departamento de Pediatría, Universidad Autónoma de Madrid, Madrid, España.
authors.forename: P
authors.initials: P
authors.lastname: Ros
authors.affiliation: Servicio de Pediatría y Unidad de Endocrinología Pediátrica, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, España.
authors.forename: E
authors.initials: E
authors.lastname: Colino-Alcol
authors.affiliation: Bambino Gesù Children's Hospital, IRCCS, Roma, Italia.
authors.forename: V
authors.initials: V
authors.lastname: Grasso
authors.affiliation: Bambino Gesù Children's Hospital, IRCCS, Roma, Italia; Department of Experimental Medicine and Surgery, University of Tor Vergata, Roma, Italia.
authors.forename: F
authors.initials: F
authors.lastname: Barbetti
authors.affiliation: Departamento de Pediatría, Universidad Autónoma de Madrid, Madrid, España; Servicio de Endocrinología y Servicio de Pediatría, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, España; CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid España. Electronic address: argentefen@terra.es.
authors.forename: J
authors.initials: J
authors.lastname: Argente
mesh_terms: D002648:Child; D003920:Diabetes Mellitus; D005260:Female; D006801:Humans; D007328:Insulin / Q000145:classification; D007333:Insulin Resistance / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011972:Receptor, Insulin / Q000235:genetics*; D012720:Severity of Illness Index; D013577:Syndrome
chemical_list: D007328:Insulin; D011972:Receptor, Insulin
keywords: Acanthosis nigricans; Acantosis nigricans; Hiperandrogenismo; Hyperandrogenism; Insulin receptor mutation; Insulin resistance; Insulinorresistencia; Mutación del receptor de insulina; Tirosinquinasa; Tyrosine kinase