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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phase three of the Quebec Cooperative Study of Friedreich's Ataxia was devoted to an understanding of the physiopathology of individual symptoms on the basis of previously discovered biochemical leads. The present paper attempts to pull these results together by presenting, as a hypothesis, a unifying scheme of possible interactions and relationships. The central core of this hypothesis is the demonstration in Friedreich's ataxia of a state of mitochondrial energy deprivation. This is indirectly responsible for such associated and important symptoms as muscle weakness, dying-back neuropathy, scoliosis and hypertrophic cardiomyopathy. Secondarily, and possibly as an independent but linked-event, the entry of glucose into cells and pyruvate oxidation, are slowed down, favoring the development of diabetes. As a consequence, tissue concentrations of glutamic acid and aspartic acid are decreased, particularly in more vulnerable areas such as the cerebellum, brain stem and dorsal root ganglia. This tissue deficiency in putative excitatory neurotransmitters is directly responsible for the symptom of ataxia. This conclusion is reinforced by the correction of the ataxia in experimental animals, by the intraventricular injection of the same amino acids, and not by the injection of other stimulants of motricity. The observed mitochondrial energy deprivation could be the metabolic consequence of major changes in the linoleic acid (18.2) composition of inner mitochondrial membrane phospholipids, such as cardiolipin. Such decreases in membrane 18:2 could be the result of interference with the normal incorporation of this fatty acid to lipoproteins and/or cell membranes. It is at this level that the search for the specific enzyme defect in Friedreich's ataxia is continuing.
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PMID:Friedreich's ataxia 1980. An overview of the physiopathology. 678 90

The authors report a case of Charcot-Marie-Tooth disease that mimicked Friedreich's ataxia and featured impaired tendon reflexes in the limbs, incoordination mimicking cerebellar disease in the extremities, extensor plantar responses on both sides, bilateral foot deformity, imparied position sense in the toes, absent vibratory sense in the distal parts of the legs and minimal distal weakness with wasting. Motor conduction velocity in the upper limbs was substantially reduced. Other cases similar in nature reported in the literature resemble spino-cerebellar degeneration in general, and Friedreich's ataxia, in particular. It is emphasized that the natural history, EMG, motor conduction velocity studies and examination of other affected members of the family permit the correct diagnosis to be made in such cases. It is also emphasized that patients similar to the one reported here may also resemble, and should be differentiated from, cases of familial dorsal column ataxia (Biemond type). Stress is put upon the fact that when Charcot-Marie-Tooth disease mimicks spino-cerebellar degeneration, substantial slowing of motor conduction in the upper limbs is generally sufficient to establish the diagnosis. The relation between Friedreich's ataxia an Charcot-Marie-Tooth disease is reviewed and it is concluded that these two disorders are distinct clinical and pathological entities.
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PMID:A case of Charcot-Marie-Tooth disease mimicking Friedreich's ataxia: is there any association between friedreich's ataxia and Charcot-Marie-Tooth disease? 710 97

Dynamic muscle function was evaluated in nine patients with Friedreich's ataxia (FA) and eight with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The measurement of torque throughout maximum voluntary isokinetic knee movements was used to quantitatively describe muscle weakness in the ataxic patients. Both FA and ARSACS patients were shown to have decreased dynamic strength in comparison to normal values during knee extension and flexion movements at 30 degrees/s. In the FA patients a lower torque-producing capacity was seen in the older patients. The electromyographic (EMG) activity was recorded in lower extremity muscles during the movements. In the vastus lateralis (VL), deviations from the normal EMG activation pattern were described in both groups of patients. A reduced amplitude in the EMG activity in the medial hamstrings (MH) was seen in the majority of the patients. An index of coactivation was defined by comparing the EMG activity when a muscle lengthened (antagonistic) to the EMG activity when the same muscle shortened (agonistic) during the isokinetic contractions. In comparison to normal values increased coactivation indexes were present in the VL and MH in patients of both groups. The characteristics of dynamic muscle strength and the activation of agonistic and antagonistic muscles described in the present study will provide the basis of evaluation for the effects of therapy in these patients.
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PMID:A preliminary study of dynamic muscle function in hereditary ataxia. 721 52

Clinical characteristics of ten patients with Friedreich's disease are presented. Two cases were members of the same family, another patient had a brother with the disease, and in two cases there was consanguinity. The dominant inheritance pattern was absent in all cases. Initial symptoms and clinical signs were present under 5 years of age in six cases, and in three of them under 2 years of age. As reported in other series, in our cases the disorder first appeared in the legs. Other early manifestations included skeletal deformities and dysarthria, as well as diplopia, paresthesias and dizziness. Friedreich's ataxia results from pyramidal tract degeneration and changes in the cerebellum. Babinski sign was present in nine patients. Other findings were: muscular weakness, distal amyotrophy and distal dystonia. Two patients suffered epileptic attacks with typical EEG pattern. Kyphoscoliosis and pes cavum were constant skeletal deformities. ECG revealed signs of myocardial ischemis in nine patients, although none of them had symptomatology of heart disease. Glucose tolerance test carried out in three cases showed diabetic curves. Results of nerve speed conduction were as follows: normal in one case; decreased sensitive speed conduction in four cases, and decrease of both sensitive and motor speed conduction in other four cases. EMG showed signs of chronic denervation in three cases. These results coincide with those published by other authors.
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PMID:[Friedreich's disease. Clinical study of ten cases (author's transl)]. 737 33

Four patients with Friedreich's ataxia took part in an open trial, in which they consumed 50-100g/day lecithin granules (containing approximately 22% phosphatidycholine) for 16 weeks, but no improvement resulted. Several unwanted effects including diarrhoea, nausea, depression, "hot flushes" and weakness were experienced. Resting levels of free-choline in plasma were within the range found in 19 normal subjects. Sixteen other patients with Friedreich's ataxia also had normal free-choline levels. Treatment with lecithin significantly increased plasma free-choline levels, but there was a trend for these to fall towards baseline levels, despite continued ingestion of lecithin.
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PMID:Effect of lecithin on disability and plasma free-choline levels in Friedreich's ataxia. 742 Jan 7

Six families are described with hereditary motor and sensory neuropathy (HMSN) of probable autosomal recessive inheritance. Four of these were classified as HMSN type I and two as type II. The consanguinity rate in this series was high, suggesting that these recessive genes are rare. In comparison with the dominantly inherited forms of these disorders, the mean age of onset was significantly earlier for the type II cases but did not differ for the type I patients. Motor nerve conduction velocity was significantly less for the type I cases but did not differ for the type II form. The recessive type I cases tended to show a greater incidence of weakness, ataxia, tendon areflexia and scoliosis than in the dominant form. The importance of differentiating such cases from Friedreich's ataxia is emphasised.
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PMID:Autosomal recessive forms of hereditary motor and sensory neuropathy. 743 Oct 27

From 1979 to 1992, 170 muscular assessments performed on 33 patients with Friedreich's Ataxia were reviewed. The average followup was 6 years. All muscle evaluations were done by the same team. It was possible to delineate a fairly regular and statistically significant pattern of slowly progressive and symmetrical loss of strength affecting mainly the lower limbs, and more specifically the pelvic girdle muscles. The first significant weakness was observed in the hip extensor group, followed in a variable fashion by other muscle groups of the lower limb. Upper limb and trunk muscles remained relatively spared until late in the disease process, with an overall strength approximately 80% of normal. Use of a wheelchair began at a mean age of 18.2 years, at which time the lower-limb strength averaged 70% of normal. Patients became totally unable to walk at a mean of age 20.5 years old, with a further decline in lower limb strength to 56% of normal. Weakness does not appear to be the primary cause for loss of ambulation in patients with Friedreich's ataxia.
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PMID:Natural history of muscle weakness in Friedreich's Ataxia and its relation to loss of ambulation. 763 85

Friedreich ataxia (FRDA) is a common autosomal recessive degenerative disease (1/50,000 live births) characterized by a progressive-gait and limb ataxia with lack of tendon reflexes in the legs, dysarthria and pyramidal weakness of the inferior limbs. Hypertrophic cardiomyopathy is observed in most FRDA patients. The gene associated with the disease has been mapped to chromosome 9q13 (ref. 3) and encodes a 210-amino-acid protein, frataxin. FRDA is caused primarily by a GAA repeat expansion within the first intron of the frataxin gene, which accounts for 98% of mutant alleles. The function of the protein is unknown, but an increased iron content has been reported in hearts of FRDA patients and in mitochondria of yeast strains carrying a deleted frataxin gene counterpart (YFH1), suggesting that frataxin plays a major role in regulating mitochondrial iron transport. Here, we report a deficient activity of the iron-sulphur (Fe-S) cluster-containing subunits of mitochondrial respiratory complexes I, II and III in the endomyocardial biopsy of two unrelated FRDA patients. Aconitase, an iron-sulphur protein involved in iron homeostasis, was found to be deficient as well. Moreover, disruption of the YFH1 gene resulted in multiple Fe-S-dependent enzyme deficiencies in yeast. The deficiency of Fe-S-dependent enzyme activities in both FRDA patients and yeast should be related to mitochondrial iron accumulation, especially as Fe-S proteins are remarkably sensitive to free radicals. Mutated frataxin triggers aconitase and mitochondrial Fe-S respiratory enzyme deficiency in FRDA, which should therefore be regarded as a mitochondrial disorder.
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PMID:Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. 932 46

We have studied a man with an atypical form of Friedreich's ataxia (FRDA), who presented at age 26 years with a 2-year history of unsteadiness and clumsiness. The predominant feature of his initial neurological examination was a spastic paraparesis, along with a mild distal weakness and hyperreflexia of the upper limbs. He also displayed limb ataxia. Frataxin GAA repeat sizes were 1,040/690. This unusual FRDA presentation is not dissimilar to that of Acadian spastic ataxia.
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PMID:Friedreich's ataxia presenting as adult-onset spastic paraparesis. 1073 7

Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.
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PMID:Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. 1158 99


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