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At least 19 recordsLinked to original sources
PubMed1985

[An autopsy case of hereditary ataxia (hereditary spastic ataxia)].

An autopsy case of hereditary spastic ataxia is reported. There are four family members with similar symptomatology through three generations. A 36-year-old man developed atactic gait at the age of 22 years, with following dysarthria, scanning speech, pyramidal signs, dysmetria, dysdiadochokinesia, nystagmus and mild sensory disturbance. The clinical course was steadily progressive and terminated about 14 years after the onset. The gross examination showed smallness of the brain stem and spinal cord with marked symmetrical atrophy of the anterior and lateral columns, especially at thoracic level. Histologically, pronounced degeneration was found in the anterior and posterior spino-cerebellar tracts, spino-thalamic tracts, and spinal ganglia. The olivary nuclei, pons and cerebellum were spared. The dentate nuclei showed considerable loss of neurons with degeneration, however there were no clinical signs related to this pathology. This case is considered to fall in the group of hereditary spastic ataxia according to Greenfield's classification, however, there was no report on degeneration of the dentate nucleus in this disease for the present. Hereditary spastic ataxia is very rare disease and only four cases have well been documented in our country to the best of our knowledge. The presence of nystagmus and superficial sensory disturbance, and sparing of the posterior column of the spinal cord seems to be common clinico-pathology in Japanese cases, differing from those of foreign cases. The fact that reactive astrogliosis was immunohistochemistry demonstrated in the degenerative regions of the spinal cord and where is no discrepancy between degenerative and reparative processes as reported before is stressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1975

Protein patterns of cerebrospinal fluid in hereditary ataxias and hereditary spastic paraplegia.

The CSF findings in hereditary ataxias and allief disorders have hitherto mostly been reported as normal if one excludes Refsum's syndrome. The CSF-protein patterns found on isoelectric focusing and quantitative paper electrophoresis were studied in 12 patients with hereditary ataxias and hereditary spastic paraplegia. Using a recently-developed technique of isoelectric focusing of CSF-proteins in flat beds of polyacrylamide gel, the authors could show abnormal CSF-protein patterns in all but 1 of the present cases. The aberrant CSF-protein patterns found showed differences between the syndromes studied. Two unique patterns with conspicuous fractions in the acid range were observed in patients with Marie-Sanger-Brown's ataxia (mother and daughter) and Holmes' ataxia. A third CSF-protein pattern was found in a sibship with Friedreich's ataxia including a double fraction in the acid region (pI 5.9-6.1) in all 4 subjects and a highly alkaline fraction (HAF) with pI about 9.3, in 3 of them. Similar acid fractions (pI 5.9-6.1) were also detected in 3 of 4 patients with hereditary spastic paraplegia, a brother and sister showing a very similar CSF-protein pattern. Double fractions with pI 5.9-6.1 and/or HAF may also occur in other neurological diseases, mostly, however, associated with other distinctive features of their CSF-protein patterns. A possibility in the future of distinguishing hereditary CNS-diseases by examination of the CSF-protein pattern is suggested.

Abetalipoproteinemia↗
PubMedDate not supplied

[The diagnostic course in patients with hereditary ataxias and hereditary spastic paraparesis].

A postal questionnaire was sent to all patients affected by hereditary ataxias and hereditary spastic paraparesis resident in the province of Turin (Italy) to study their diagnostic process. A 61% response rate was obtained. The mean time interval between onset and diagnosis was 6 years (1 to 32 years). The percentage of late diagnoses dropped from 59% before 1959 to 19% after 1970, mostly because a reduction of the interval between symptom onset and the first contact with the general practitioner. The onset with dysarthria and ataxia led to earlier neurologic consultation, but the whole time requested for the diagnosis was not modified. A reduction of the time needed for the diagnostic process may be important to address the family to an early genetic counselling.

Age Factors↗
PubMed1994

Molecular genetics of hereditary ataxias.

The hereditary ataxias are a very heterogeneous group of disorders characterized by cerebellar dysfunction that can be either isolated or accompanied by other neurological manifestations. The classification of the hereditary ataxias based on clinical or histopathological findings has been difficult because of the significant overlap of phenotypes among the various genotypes. The patterns of inheritance observed in ataxias include autosomal dominant, autosomal recessive and X-linked. Friedreich's ataxia, the most frequent form among the recessive ataxias, has been mapped to the long arm of chromosome 9 based on close linkage to the markers D9S5 and D9S15. This close linkage allows the use of these two DNA markers for prenatal diagnosis in families with one affected offspring. In the past year, significant research progress has been accomplished by applying molecular genetic studies to the dominantly inherited spinocerebellar ataxias. Spinocerebellar ataxia type 1 (SCA1), which maps to the short arm of chromosome 6, has been found to be caused by expansion of an unstable trinucleotide (CAG) repeat. This mutational mechanism explains the presence of the clinical phenomenon of anticipation in some families with SCA1. The finding of an unstable repeat in SCA1 will facilitate the diagnosis of SCA1 in familial and isolated cases and will allow preclinical and prenatal diagnosis in families with this disease. In addition to the cloning of the SCA1 gene, two dominantly inherited ataxias have been genetically mapped: SCA2, to the long arm of chromosome 12, and Machado-Joseph disease (MJD), to the long arm of chromosome 14. Given that anticipation has been observed in patients with SCA2 and MJD, it is likely that trinucleotide repeat expansion could be a common mechanism involved in all the spinocerebellar ataxias. Last, significant research progress has been accomplished in the field of hereditary ataxias associated with DNA repair defects which should facilitate our understanding of mechanisms involved in cerebellar degeneration.

Ataxia↗
PubMed1994

Infantile onset spinocerebellar ataxia represents an allelic disease distinct from other hereditary ataxias.

Hereditary ataxias are a heterogeneous group of progressive neurodegenerative disorders characterized by symptoms and signs originating mainly in the CNS. A new representative of this disease group is infantile onset spinocerebellar ataxia, an autosomal recessively inherited syndrome so far reported only in the genetically isolated Finnish population. The etiology of hereditary ataxias still remains unknown, but the gene loci behind many of them have been mapped to different chromosomal regions. We have carried out linkage analyses with markers on the regions of the previously identified ataxia loci to determine whether the infantile onset spinocerebellar ataxia syndrome represents the same allelic disease as any of the previously identified hereditary ataxias. Here we report that the infantile onset spinocerebellar ataxias syndrome does not segregate with any of the markers closely linked to the other hereditary ataxias. Consequently, it represents a genetically distinct disease, the gene locus of which still has to be identified.

Age of Onset↗
PubMed1999

[New insights in the molecular genetics and pathophysiology of hereditary ataxias].

The hereditary ataxias are a heterogeneous group of inherited neurodegenerative disorders characterised by progressive ataxia that results from degeneration of the cerebellum and its afferent and efferent connections. With respect to the pathogenic mechanisms, the hereditary ataxias may be tentatively divided into three groups: (1) The recessive ataxias are induced by the functional impairment of a protein that is essential for the survival of specific neurons while the autosomal dominant ataxias are either caused by (2) mutations of genes coding for ion channels thus resulting in a channelopathy or by (3) a novel deleterious function of a extended polyglutamine sequence within the proteins encoded by the respective genes.

Adolescent↗
PubMed1995

Clinical aspects of hereditary ataxias.

The hereditary ataxias are a group of complex genetic disorders the understanding of which is undergoing a revolution because of advances in molecular genetics. Within the last few years, at least seven different gene loci have been found to be responsible for these syndromes, and the search is on for additional loci that undoubtedly exist. This review summarizes the clinical features of the various hereditary ataxias with known gene loci, as well as others that are now defined on a clinical basis. It also deals with some of the imaging and neuropharmacologic advances that have been made in this group of disorders.

Adult↗
PubMed1997

[Genetic diagnosis, classification and clinical hereditary ataxia disease entities].

Hereditary ataxias are a heterogeneous group of neurodegenerative diseases. Neither the clinical features nor the findings at autopsy provide a satisfactory basis for the isolation of distinct categories and classification. Recently, several gene loci responsible for inherited ataxias have been identified. For several hereditary ataxias even the disease causing mutations have been described. These findings lead to a new classification of the inherited ataxias based on genotypes rather than pathology or phenotypes. Such a classification will potentially gain wide acceptance since it derives from the molecular genetic cause of the diseases. Furthermore, recent advances in molecular biology improved the understanding of the clinical variability of hereditary ataxias that occurs even within the same family. All forms of progressive dominant ataxias are most likely caused by the same type of mutation: an unstable and expanded trinucleotide repeat. The repeat expansion is moderate in patients with later onset and mild progression but is extensive in juvenile cases with a more rapid course of the disease. Furthermore, the extent of the expansion seems to be at least partially responsible for the development of different phenotypes. The identification of gene loci and mutations allows reliable diagnosis even at a presymptomatic or prenatal stage for an increasing number of inherited ataxias. Although molecular genetics has improved the diagnosis and understanding considerably for most forms of hereditary ataxias a causal therapy is still missing. Therefore, it is essential that presymptomatic analysis is always performed according to the international guidelines. They include genetic counselling by a team of experienced neurologists, geneticists, psychologists and social workers.

Chromosome Mapping↗
PubMed1990

Hereditary ataxias: epidemiological aspects.

Hereditary ataxias, hereditary spastic paraplegia and Charcot-Marie-Tooth syndrome (HA) are chronic progressive neurological diseases. Epidemiologic studies of these disorders are few. In a geographically well-defined Danish population, we present incidence rates, cumulated incidence rates and prevalence for patients with HA based on modern continuous-time survival analysis techniques. From these, prevalence has been estimated to be 6.06 per 10(5) in the 10 to 50-year-old population. Combined risk of HA was found to be 0.16% for women and 0.20% for men up to their 51st birthday.

Adolescent↗
PubMed1998

Genes involved in hereditary ataxias.

The hereditary ataxias are a group of inherited neurodegenerative disorders characterized by progressive ataxia that results from degeneration of the cerebellum and its afferent and efferent connections. Recent molecular research has led not only to the discovery of a number of causative mutations, but also shed light on the likely mechanisms by which these mutations cause the respective phenotypes. In Friedreich's ataxia (FRDA), the most common type of autosomal recessive ataxia, the loss of a mitochondrial protein, frataxin, results in overload of mitochondrial iron and oxidative stress. The autosomal dominant ataxias, spinocerebellar ataxia type I (SCAI), SCA2, SCA3 and SCA7, are caused by inheritance of an unstable, expanded CAG trinucleotide repeat. These disorders are assumed to be due to a novel deleterious function of the extended polyglutamine sequences within the proteins encoded by the respective genes. Recent observations in transgenic mice and in human post-mortem tissue suggest that the extended proteins are transported into the nucleus of neurons where they form intranuclear inclusions that disrupt normal nuclear function. In another group of dominant disorders, episodic ataxia type I and type 2 (EA-I, EA-2) and SCA6, the mutations affect genes that code for ion channels.

Animals↗
PubMed1989

Hereditary ataxia.

The hereditary ataxias, also referred to as the spinocerebellar degenerations, comprise a series of clinical manifestations that include ataxia and dysmetria, resulting from the predominant involvement of the cerebellum and its afferent and efferent pathways. These disorders are system degenerations; many of them are specific entities clearly inherited as autosomal dominant or autosomal recessive traits. Although the clinical manifestations and neuropathologic findings of cerebellar disease dominate the spinocerebellar degenerations, there may also be characteristic changes in the basal ganglia, optic atrophy, retinitis pigmentosa, or peripheral nerve disease. There are many gradations from pure cerebellar manifestations to mixed cerebellar and brain-stem disorders, cerebellar and basal ganglia syndromes, and spinal syndromes or peripheral nerve disease. The clinical picture may be consistent in one family, but sometimes there is a characteristic syndrome in the majority of family members and an entirely different disorder in one or several members.

Chromosome Mapping↗
PubMedDate not supplied

[Epidemiology of Cuban hereditary ataxia].

INTRODUCTION: The hereditary ataxias in Cuba make up the highest concentration of these patients in the world. The spinocerebellar ataxia type 2 (SCA2) molecular form is predominant. OBJECTIVES: To determine the prevalence and incidence of hereditary ataxias. PATIENTS AND METHODS: We made a descriptive study of 440 patients and 1,633 members of families at risk from this disorder in the province of Holguín. We calculated the prevalence rate and incidence. RESULTS: The rate of prevalence of patients in the province is 43 cases per 100,000 inhabitants; the highest rate was 503 cases per 100,000 inhabitants in part of the municipality of Baguanos. The age group that was most affected was that of 30-39 years, with a prevalence of 63.97 cases per 100,000 inhabitants. The rural population showed the highest incidence (62.04 cases per 100,000 inhabitants). The risk of members of affected families showing the disorder was 159.33 cases per 100,000 inhabitants in this province. The highest incidence was 18.08 cases per 100,000 inhabitants in Cacocum, where the incidence in the province was 4.39. CONCLUSIONS: On average the disorder passes from one state to the next every year, which suggests that the extent of the disorder worsens with time. The prevalence and incidence are the highest in the world. This together with the dominant pattern of inheritance, the effect of anticipation and inexorably progressive course of the disorder shows the serious health problem that affects the Eastern region of Cuba.

Adult↗
PubMed1991

[Clinical and genetic analysis of 188 families with spinocerebellar degeneration. Friedreich's disease and P. Marie's hereditary ataxias].

Based on the hereditary ataxias concepts and a large field survey, the authors analyzed 392 cases of spino-cerebellar degeneration belonging to 188 families. Two main clinical groups were identified: 227 cases of Friedreich ataxia and 74 cases of cerebellar hereditary ataxia of P. Marie type. The association in the same patient of peroneal atrophy of Charcot Marie type with Friedreich ataxia (17 cases) or P. Marie cerebellar hereditary ataxia (13 definite cases and 13 probable) was the most striking finding. "Forme fruste", incomplete form or complex form of Friedreich ataxia were present in some families while in some others there was spastic paraplegia or pure Charcot Marie Tooth disease. This clinical heterogeneity in families of spino-cerebellar degeneration is discussed.

Cerebellar Ataxia↗
PubMed1978

Computerized tomography in hereditary ataxias.

Thirty-nine patients with hereditary ataxia (HA), hereditary spastic paraplegia or Charcot-Marie-Tooth disease were investigated with computerized cranial tomography (CT). Infratentorial as well as supratentorial atrophies were registrated and scored. These were compared with the patient's neurological symptoms, which were related to the lesion in the central nervous system, and scored. There was correlation between the distribution of brainstem/cerebellar symptoms and the distribution and degree of infratentorial atrophy. HA cases with cerebral cortical atrophy had significantly higher dementia scores than those without wide sulci. Intravenous injection with contrast medium was of no diagnostic aid, as no focal changes were found. It is concluded that CT is an aid in the diagnosis of hereditary ataxias and hereditary spastic paraplegia.

Adult↗
PubMedDate not supplied

[Hereditary ataxias].

INTRODUCTION AND OBJECTIVE: The hereditary ataxias form a large, complex group of entities whose recognition is essential for correct genetic assessment, satisfactory clinical control and in some cases a suitable therapeutic approach. The clinico-semiological variety and advances in molecular biology have made the hereditary ataxias one of the most interesting subjects in neurology. In this paper our objective is to classify the clinical approach of the hereditary ataxias and define the different conditions known so as to orientate complementary investigations and thus obtain the correct diagnosis. DEVELOPMENT AND CONCLUSION: We analyze and classify them, according to their mode of presentation, as congenital (in general nonprogressive) and progressive. Both groups are then divided according to how they are inherited and we also include the specific molecular findings.

Diagnosis, Differential↗
PubMed1998

Molecular genetics of the hereditary ataxias.

One of us (MP) learned about the mapping of Huntington disease gene to chromosome 4 from the late Dr. Anita Harding. She got the news over the phone from her London office during a visit to Italy for a meeting on hereditary ataxias. In Britain, they receive Nature at least a week earlier than us. Dr. Harding was very excited, and she immediately said that that was the way to go if we wanted to understand the causes of hereditary ataxias, classify these diseases in a rational way, and eventually find a treatment. At that time, the challenge seemed, and indeed was, formidable. No clue was then available about the genetic basis of what Dr. Harding aptly called "hereditary ataxias of unknown cause," their classification was confused and controversial, and all attempts to find specific biochemical abnormalities had failed. Fourteen years later, the success of the molecular genetic studies is astounding. The defective genes have been identified for Friedreich ataxia, the major recessive "hereditary ataxia of unknown cause," and for five dominantly inherited "hereditary ataxias of unknown cause." Three more dominant ataxia genes have been mapped. The molecular pathogenesis of the dominant ataxias begins to be unraveled and animal models have been and are being developed. Information is also quickly accumulating about the defective protein in Friedreich ataxia. Direct molecular diagnosis is now possible. Classification has been revolutionized. Diagnostic criteria are being redefined in the light of the molecular discoveries. The goal of this review, dedicated to the memory of the late Dr. Harding, is to offer a concise summary of current knowledge about the molecular genetics of some of the hereditary ataxias that used to be classified as of "unknown cause."

Ataxia↗