Genetic disorder with hypogonadism and progressive
Cerebellar Ataxia and Hypogonadotropic Hypogonadism;
Deficiency of Luteinizing Hormone-Releasing Hormone with Ataxia.
Gordon Holmes (1876-1966), an English neurologist, described this autosomal-recessive transmitted
syndrome almost 100 years ago.
Only a few case reports exist,
and the underlying pathophysiology is not completely clear.
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
Although no case reports on this disease
in association with anesthesia exist, it is probably best to apply the same
precautions as in Friedreich ataxia with regard to muscle relaxants
(however, cardiomyopathy has not been described in Gordon Holmes syndrome).
The use of a peripheral nerve
stimulator during induction is essential to titrate the relaxants to effect
and to closely monitor recovery. Because different muscle groups may be
affected differently by the disease, it might be necessary to monitor
(residual) paralysis in more than one site.
Succinylcholine may elicit a hyperkalemic
response, and the sensitivity to nondepolarizing drugs may be altered.
Holmes G: A form of familial degeneration of the cerebellum. Brain 30:466,
Seminara SB, Acierno JS Jr, Abdulwahid NA, et al: Hypogonadotropic
hypogonadism and cerebellar ataxia: Detailed phenotypic characterization of
a large, extended kindred. J Clin Endocrinol Metab