Hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis, and renal malformation syndrome.
OBJECTIVE
The aim of this study was the endocrinological, enzymatic, and genetic evaluation of a family with a complex syndrome associating hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis and renal malformation.


METHODS
Hypothalamic-pituitary-testicular function, olfaction, steroid sulphatase activity, and morphological renal studies were assessed. DNA molecular analyses were carried out in all the patients.


METHODS
Two brothers and their maternal uncle showed the clinical picture of congenital ichthyosis, hypogonadism, hyposmia and unilateral renal maldevelopment.


METHODS
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 sulphatase activity. DNA amplification analysis and Southern blot analysis of four Xp22.3 loci were performed.


RESULTS
Low levels of gonadotophins, basally 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 aplasia were demonstrated. A large Xp 22.3 deletion including the genes responsible for X-linked ichthyosis (steroid sulphatase deficiency) and Kallmann syndrome was demonstrated.


CONCLUSIONS
The absence of the gene encoding steroid sulphatase accounts for the X-linked ichthyosis in these patients, whereas the absence of the Kallmann syndrome gene accounts for hypogonadism, anosmia and for the single kidney found in two of the three patients.
Martul
P
P
Division of Pediatric Endocrinology, Hospital de Cruces, Bilbao, Spain.
Pineda
J
J
Levilliers
J
J
Vazquez
J A
JA
Rodriguez-Soriano
J
J
Loridan
L
L
Diaz-Perez
J L
JL
D000293:Adolescent; D000328:Adult; D001192:Arylsulfatases / Q000097:blood; D001483:Base Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D005640:Follicle Stimulating Hormone / Q000097:blood; D005784:Gene Amplification; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000235:genetics*; D016114:Ichthyosis, X-Linked / Q000097:blood / Q000235:genetics*; D007668:Kidney / Q000002:abnormalities*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D000857:Olfaction Disorders / Q000097:blood / Q000235:genetics*; D043266:Steryl-Sulfatase; D013577:Syndrome; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA; D001192:Arylsulfatases; D043266:Steryl-Sulfatase