Les diabètes insipides néphrogéniques héréditaires

Abstract

Les malades atteints de diabète insipide néphrogénique héréditaire excrètent de grandes quantités d'urines diluées. Les tubules collecteurs rénaux sont résistants à l'action de l'hormone antidiurétique (arginine-vasopressine, AVP) et le mécanisme de concentration des urines est atteint. Dans 90 % des cas, la maladie, liée à l'X, est due à des mutations du récepteur de l'arginine-vasopressine qui affectent la première étape de la transmission du signal aboutissant au transport de l'eau. Dans 10 % des cas, la maladie est liée à des mutations du gène de l'aquaporine II impliquée dans la dernière étape du transport de l'eau. Cette maladie, de découverte récente, est autosomique récessive : les garçons et les filles sont atteints de manière égale. Le diagnostic précoce est fondamental car il permet, malgré l'absence actuelle de tout traitement, d'éviter les épisodes de déshydratation qui peuvent entraîner un retard staturo-pondéral et un déficit intellectuel irréversible.

In congenital nephrogenic diabetes insipidus, the renal collecting ducts are resistant to the antidiuretic action of arginine-vasopressin, or to its antidiuretic analogue, dDAVP. This is a rare, but now well described entity secondary to either mutations in the AVPR2 gene that codes for the vasopressin antidiuretic (V2) receptor or to mutations in the AQP2 gene that codes for the vasopressin dependent water channel. Of 75 families with congenital nephrogenic diabetes insipidus referred to our laboratory in Montreal, 71 families had AVPR2 mutations and four had AQP2 mutations. The AVPR2 gene is located in chromosome region Xq28 and, as a consequence, males with an AVPR2 mutation have a phenotype characterized by early dehydration episodes, hypernatremia and hyperthermia as early as during the first week of life. The dehydration episodes can be so severe as to lower arterial blood perfusion pressure to a degree that is not sufficient to sustain adequate oxygenation in brain, kidneys and other organs. Mental and physical retardation and renal failure are the classical 'historical' consequences of a late diagnosis and lack of treatment. Seventy-two different putative disease-causing mutations in the AVPR2 gene have been reported in 102 unrelated families with X-linked nephrogenic diabetes insipidus. This diversity of mutations and the rarity of the disease is consistent with ani X-linked recessive disease, lethal in the past for male patients, and balanced by de novo mutations. The AQP2 gene is located in chromosome region 12q13. Males and females affected with congenital nephrogenic diabetes insipidus are either homozygous for a mutation in the AQP2 gene or carry two different mutations. The onset and severity of the clinical manifestion tions of autosomal recessive nephrogenic diabetes insipidus are similar to those of X-linked nephrogenic diabetes insipidus. We encourage physicians who follow families with hereditary nephrogenic diabetes insipidus to recommend molecular genetic analysis because early diagnosis and treatment of infants can avert the physical and mental retardation associated with episodes of dehydration. [References: 26]