COEXISTENCE OF HUNTINGTONS-DISEASE AND FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS - CASE PRESENTATION

We present the clinical, molecular genetic and neuropathological findi ngs of an sl-year-old man with concurrent Huntington's disease (HD) an d familial amyotrophic lateral sclerosis (FALS). His mother had been d iagnosed clinically as having ALS. There was no known family history o f HD, but a maternal uncle had died in a chronic care psychiatric hosp ital. The diagnosis of HD in the patient was suspected at age 66, afte r 8 years of personality change, hallucinations, agitation, cognitive decline and choreoathetosis. No symptoms of motor neuron disease were noticed at that time, but progressive weakness developed later. Postmo rtem examination revealed cerebral atrophy, marked atrophy of basal ga nglia (grade 3), and atrophy of brain stem and spinal cord. The neostr iatum displayed massive neuronal loss and gliosis. The neocortex showe d changes characterisitic of Alzheimer's disease. Pathological lesions also included loss of neurons and gliosis in the anterior hems, Clark e's columns and the hypoglossal nuclei; degeneration of the lateral co rticospinal tracts, dorsal spinocerebellar tracts and fasciculus graci lis; and rare Bunina bodies and ubiquitin-positive filamentous skeins in motor-neuron perikarya. Molecular analysis demonstrated chromosome 4p16.3 expansion of trinucleotide repeats characteristic of HD. Analys is of Cu,Zn superoxide dismutase gene and heavy neurofilament subunit gene failed to demonstrate mutations. The concurrence of HD and FALS i n our patient and three previously reported cases did not appear to be associated with cosegregation in other family members.