Azorean Disease of the Nervous System

Abstract

We studied a family of Portuguese ancestry from the Azores who suffered a progressive neurologic disease characterized by gait ataxia, features similar to Parkinson's disease in some patients, limitation of eye movements, widespread fasciculations of muscles, loss of reflexes in the lower limbs, followed by nystagmus, mild cerebellar tremor and extensor plantar responses. Two post-mortem examinations revealed loss of neurons and gliosis in the substantia nigra, nuclei pontis (and in the putamen in one case) as well as in the nuclei of the vestibular and other cranial nerves, columns of Clarke and anterior horns, in the spinal cord there were also loss of fibers in the fasciculi gracilis and mild changes in the pyramidal tracts. Comparison of the disease in this family with the findings reported in three families of similar ancestry, previously thought to have different disorders, suggests that they may all represent a single genetic entity with variable expression.

A Prospective Study of 50 Cases of Familial Parkinson’s Disease

“…4 and described in the legend. Although we did not encounter the following entities in our own series, it is well known that cases of Parkinsonism could also occur in association with olivo-ponto-cerebellar atrophy, and in the so-called "Joseph disease" of the Azores (Romanul et al, 1977). In all these instances it appears that the presence of the underlying genetic entity is a predisposing factor to the development of the Parkinsonian state.…”

Motor uncoordination and neuropathology in a transgenic mouse model of Machado–Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products

“…The pathological hallmark of the disease is the presence of nuclear inclusions of aggregation-prone expanded ATXN3 in the patients' brains. Although ATXN3 is ubiquitously expressed (Paulson et al, 1997), only restricted neuronal populations of the central nervous system (CNS) are classically described as affected, namely the cerebellar dentate nucleus, pallidum, substantia nigra, thalamus, subthalamic, red, and pontine nuclei, cranial nerve nuclei and the anterior horn and Clarke's column of the spinal cord (Romanul et al, 1977;Rosenberg et al, 1976;Woods and Schaumburg, 1972). Recent pathological studies have suggested that the extension of CNS degeneration in MJD patients at end stages may be more widespread, including the visual, auditory, vestibular, somatosensory, ingestion-related, dopaminergic and cholinergic systems (Rub et al, 2008).…”

Diagnóstico de Ataxia Espinocerebelosa tipo 3 (Enfermedad de Machado-Joseph) en Chile

“…De las ataxias heredadas en forma dominante (más de 30 tipos ya descritos) la más frecuente a nivel mundial es la enfermedad de Machado-Joseph (el gen fundador es de origen portugués) llamada también ataxia espinocerebelosa tipo 3 [1][2][3][4] . Fue descrita en 1972 en Estados Unidos en 3 familias de apellidos Machado, Joseph y Thomas, emigrantes de origen en las islas Azores, Portugal 5,6 .…”