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Coexistence of Huntington's disease and familial amyotrophic lateral sclerosis: case presentation
A Rubio1, K Steinberg, D A Figlewicz
1Department of Pathology, University of Rochester, NY 14642, USA. arubio@pathology.rochester.edu
Insights
This study details a rare case of concurrent Huntington's disease (HD) and familial amyotrophic lateral sclerosis (FALS) in an 81-year-old man, confirmed by molecular and neuropathological findings.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Familial amyotrophic lateral sclerosis (FALS) and Huntington's disease (HD) are distinct neurodegenerative disorders.
- Concurrent diagnoses are exceptionally rare, posing diagnostic and research challenges.
Observation:
- An 81-year-old male presented with symptoms suggestive of HD, including cognitive decline and choreoathetosis, followed by motor neuron disease symptoms.
- Neuropathological examination revealed characteristic lesions of HD in the basal ganglia and Alzheimer's disease in the neocortex.
- Spinal cord and brainstem pathology confirmed motor neuron degeneration consistent with ALS.
Findings:
- Molecular analysis confirmed a trinucleotide repeat expansion on chromosome 4p16.3, diagnostic of HD.
- No mutations were found in the Cu,Zn superoxide dismutase or heavy neurofilament subunit genes.
- The co-occurrence of HD and FALS in this patient and three prior cases showed no clear cosegregation pattern within families.
Implications:
- This case highlights the possibility of co-occurring neurodegenerative diseases.
- Understanding the interplay between different genetic and pathological mechanisms in such cases is crucial for future research.
- Further investigation is needed to determine if there are shared genetic or environmental factors contributing to the concurrence of HD and FALS.
Abstract:
We present the clinical, molecular genetic and neuropathological findings of an 81-year-old man with concurrent Huntington's disease (HD) and familial amyotrophic lateral sclerosis (FALS). His mother had been diagnosed clinically as having ALS. There was no known family history of HD, but a maternal uncle had died in a chronic care psychiatric hospital. The diagnosis of HD in the patient was suspected at age 66, after 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. Postmortem examination revealed cerebral atrophy, marked atrophy of basal ganglia (grade 3), and atrophy of brain stem and spinal cord. The neostriatum displayed massive neuronal loss and gliosis. The neocortex showed changes characteristic of Alzheimer's disease. Pathological lesions also included loss of neurons and gliosis in the anterior horns, Clarke's columns and the hypoglossal nuclei; degeneration of the lateral corticospinal tracts, dorsal spinocerebellar tracts and fasciculus gracilis; 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. Analysis of Cu,Zn superoxide dismutase gene and heavy neurofilament subunit gene failed to demonstrate mutations. The concurrence of HD and FALS in our patient and three previously reported cases did not appear to be associated with cosegregation in other family members.