The first symptoms are that of hypogonadotropic
hypogonadism, although there seems to be a broad clinical spectrum of this
disease as patients with hypergonadotropic hypogonadism have been described
as well. A defect in the production or the release of gonadotropins in the
pituitary gland is responsible for the hypogonadotropic state. Most often,
plasma concentrations of luteinizing hormone and follicle-stimulating
hormone fail to rise after repetitive stimulation with
gonadotropin-releasing hormone, which is consistent with a primary pituitary
defect. However, a small number of patients do respond to exogenous
gonadotropin-releasing hormone, suggesting a primary hypothalamic
disturbance. Usually, in the third to fourth decade of life, progressive
cerebellar ataxia and profound dementia develop, resulting in patients who
are bedridden with no purposeful movements and finally death secondary to
aspiration pneumonia. CT and/or MRI scans may reveal marked cerebellar and,
to a lesser degree, cortical atrophy, as well as hypodensities in the
cerebral white matter. Spasticity and nystagmus are not features of this
disorder.