ABSTRACT
Los síndromes monogénicos de insulinorresistencia sin lipodistrofia constituyen un rupo de entidades infrecuentes que incluyen los síndromes de Donohue o leprechaunismo, Rabson-Mendenhall y resistencia a la insulina tipo A. Se caracterizan por un amplio espectro fenotípico que asocia insulinorresistencia extrema y alteraciones hidrocarbonadas de grado variable. Presentamos un caso de resistencia a la insulina tipo A, caracterizado por resistencia insulínica grave, acantosis nigricans e hiperandrogenismo, debido a una mutación en heterocigosis en el xón 19 del gen del receptor de insulina que codifica para el dominio tirosinquinasa. Se destaca la elevada morbilidad de dicha entidad, a pesar de incluirse dentro del espectro menos grave de los síndromes genéticos de resistencia insulínica, así como la ausencia de una terapia satisfactoria. El estudio molecular revela el diagnóstico e informa del pronóstico y la supervivencia, factores ligados a la función residual del receptor, además de contribuir al desarrollo de nuevas dianas terapéuticas
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
