Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three brothers in a family with Val30Met transthyretin (TTR) amyloid polyneuropathy (FAP) in Iiyama, Japan were studied pathologically. In this family, affected members have been reported to show typical clinical features of FAP, and some have been documented to exhibit symptoms and signs of central nervous system (CNS) involvement consisting of cerebellar ataxia and pyramidal tract signs. After the original description, this family was regarded as a unique phenotype of this form of FAP; however, subsequent molecular genetic studies revealed that some patients and asymptomatic members in the family had Val30Met TTR and/or spinocerebellar ataxia type 1 (SCA1) gene mutations. In this study, pathological examination of two patients with both FAP and CNS symptoms showed (1) TTR-immunoreactive leptomeningeal and cerebrovascular amyloid deposition compatible with Val30Met TTR FAP, and (2) neuronal loss and gliosis mainly in the Purkinje cell layer, spinocerebellar system, olivo-ponto-cerebellar system, dentato-rubral system, gracile nuclei, cuneate nuclei, and various nuclei of cranial nerves, accompanied by anti-expanded polyglutamine tract antibody positive neuronal intranuclear inclusions, all of which were compatible with the pathological findings of SCA1. On the other hand, the remaining patient with FAP symptoms only showed the former pathological finding alone. The present study demonstrates, at the pathological level, that Val30Met TTR FAP and SCA1 coexist in the same family members, and that the CNS dysfunction seen in the patients in this family is ascribable to SCA1 pathology but not to CNS amyloidosis.
 ...
PMID:Coexistence of familial transthyretin amyloidosis ATTR Val30Met and spinocerebellar ataxia type 1 in a Japanese family--a follow-up autopsy report. 1552 22

Prion diseases are typically recognized as rapidly progressive dementing illnesses that also feature myoclonus and cerebellar ataxia. Several families have now been described with a late-onset hereditary sensory and autonomic neuropathy caused by truncation of prion protein (PrP), and associated with systemic amyloidosis, which was a profoundly unexpected phenotype. The chronic symptoms of this disorder, termed PrP systemic amyloidosis, can be very disabling, and are comparable to familial amyloid polyneuropathy (FAP) caused by transthyretin mutations. Patients require symptomatic therapies directed towards control of nausea, diarrhoea, incontinence, neuropathic pain and postural hypotension. Although the potential transmissibility of this new prion disease is probably extremely low, we advocate PrP gene analysis before biopsy in the investigation of peripheral and autonomic neuropathies, or for patients with unexplained diarrhoea and neuropathy. Prion diseases and the FAPs both display prominent effects of mutation type on clinical presentation and patterns of pathology-a fascinating but unexplained observation. Several neurodegenerative diseases associated with central protein misfolding, such as Huntington and Parkinson diseases, also have under-recognized peripheral components. Most of the familial amyloidoses can be explained by known gene mutations, but amino acid variants in proteins involved in other central neurodegenerative diseases might direct the initial pathology to the periphery.
...
PMID:A new prion disease: relationship with central and peripheral amyloidoses. 2562 92