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Genetic disorder with hypogonadism and progressive cerebellar ataxia.

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 disorder.

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, 1907.
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 87:1607, 2002.  [PubMed: 11932290]

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