Adrenomyeloneuropathy
Incidence
X-linked inheritance.
Clinical Characteristics
Characteristically, a man in his twenties, who previously had been well, notes stiffness or clumsiness in his legs. Generalized weakness, weight loss, pigmentation, and attacks of nausea and vomiting may have been noted before, after, or concurrent with the neurologic symptoms, leading to a diagnosis of Addison disease. The neurologic disability is slowly progressive, so that within the next 5 to 15 years the gait disturbance becomes severe and requires the use of a cane or a wheelchair. Voiding disturbances are noted in the twenties or thirties. Somatosensory and brain-stem auditory evoked responses are nearly always abnormal, whereas visual evoked responses and peripheral nerve abnormalities occur less frequently. The cerebrum is involved to a variable extent in AMN. The brain MRI and cognitive function are abnormal in approximately half of the AMN patients. These patients represent an "AMN-cerebral" subgroup, whereas those without cerebral involvement are referred to as "pure AMN." Probably the pure AMN group has a more favorable prognosis, with some patients surviving to the eighth decade. Some AMN patients deteriorate rapidly once cerebral involvement becomes evident, then resembling the course of the childhood or adult cerebral form of adrenoleukodystrophy. Neurologic examination reveals a spastic paraparesis with the upper extremities usually intact. Impaired vibration sense in the distal lower extremities and long tract signs with a relatively mild peripheral neuropathy are noted. Motor conduction velocity may be reduced in the lower extremities. Intellectual function usually appears intact, but detailed psychological tests may detect cognitive defects that may progress as the disease advances. Depression or emotional disturbances are frequent and become more severe as the illness advances. Impotence beginning in the late twenties or thirties is common in AMN patients. In one patient, hypogonadism preceded by 12 years the other manifestations of AMN. In spite of the eventual impairment of sexual function, AMN patients often have children. Survey of 76 men with Adrenomyeloneuropathy (AMN) showed the following abnormalities in %: Cognitive function: 42, Brain-stem auditory evoked: 98, Visual evoked potentials: 24, Somatosensory evoked potentials: 100, Peroneal nerve velocity: 68, Median nerve velocity: 14, Brain MRI: 46, Cerebral white matter affected as follows: Parietooccipital:28, Temporal: 43, Frontal: 11, Corpus callosum:17, Visual pathways: 39, Auditory pathways: 29, Corticospinal tract: 41, Cerebellar white matter: 11, Cerebral atrophy:16, Overall abnormality: 46%. Some men who develop AMN have shown hyperpigmentation since early childhood. At the time that AMN is diagnosed, plasma ACTH levels usually are greatly elevated. Presumably, these men had abnormally high ACTH (and melanocyte-stimulating hormone) levels and in this way were able to maintain relatively normal adrenal function during infancy and childhood. In the Kennedy Krieger Institute series, adrenal insufficiency preceded neurologic deficit in 42 percent of AMN patients. In two patients, Addison disease preceded neurologic dysfunction by 22 and 27 years. One-third of AMN patients have normal adrenal function, and this is the group in which the diagnosis of AMN is most likely to be missed. The differential diagnosis of AMN includes: multiple sclerosis, familial spastic paraparesis, spinocerebellar or cerebellar degeneration, cervical spondylosis and spinal cord tumor. The clinical effects in AMN are more difficult to assess, because the rate of progression of the illness in untreated patients is slow and variable. Preliminary data suggest that the therapy does not alter the slow progression of disability. In 70 AMN patients who were being treated with GTE-GTO, normalization or greater than 50 percent reduction of plasma VLCFA levels was achieved in 60 percent of the patients. None showed improvement of VER, and 23 percent showed poorer VER.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Elevated plasma VLCFA levels. The following tests tend to be abnormal: Brain-stem auditory evoked: 98%, Visual evoked potentials: 24%, Somatosensory evoked potentials: 100%, Peroneal nerve velocity: 68%, Median nerve velocity: 14%, Brain MRI: 46%. 2/3 of patients have abnormal adrenal function when stimulated with ACTH. One-third of AMN patients have normal adrenal function, and this is the group in which the diagnosis of AMN is most likely to be missed.