HYPOGONADOTROPIC HYPOGONADISM WITH HYPOSMIA, X-LINKED ICHTHYOSIS, ANDRENAL MALFORMATION SYNDROME

OBJECTIVE The aim of this study was the endocrinological, enzymatic, a nd genetic evaluation of a family with a complex syndrome associating hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis and renal malformation. DESIGN Hypothalamic-pituitary-testicular function, olfaction, steroid sulphatase activity, and morphological renal studi es were assessed, DNA molecular analyses were carried out in all the p atients. PATIENTS Two brothers and their maternal uncle showed the cli nical picture of congenital ichthyosis, hypogonadism, hyposmia and uni lateral renal maldevelopment. MEASUREMENTS LH and FSH were determined by RIA basally and after GnRH stimulation, and the test repeated after a period of GnRH priming. Testosterone response to hCG was measured. Arylsulphatase C assay was performed as a measure of steroid sulphatas e activity. DNA amplification analysis and Southern blot analysis of f our Xp22.3 loci were performed. RESULTS Low levels of gonadotophins, b asally and after acute GnRH, increased clearly after GnRH priming. Low testosterone levels increased promptly after hCG. Subnormal levels of arylsulphatase C were detected. Hyposmia and renal hypoplasia or apla sia were demonstrated. A large Xp 22.3 deletion including the genes re sponsible for X-linked ichthyosis (steroid sulphatase deficiency) and Kallmann syndrome was demonstrated. CONCLUSIONS The absence of the gen e encoding steroid sulphatase accounts for the X-linked ichthyosis in these patients, whereas the absence of the Kallmann syndrome gene acco unts for hypogonadism, anosmia and for the single kidney found in two of the three patients.