Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008489 (chorea)
 2,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen cases are described, including 12 cases from three different families and 7 nonfamilial cases, in which multisystem neurological disease was associated with acanthocytosis in peripheral blood and normal plasma lipoproteins. Mild acanthocytosis can easily be overlooked, and scanning electron microscopy may be helpful. Some neurologically asymptomatic relatives with significant acanthocytosis were identified during family screening, including some who were clinically affected. The mean age of onset was 32 (range 8-62) yrs and the clinical course was usually progressive but there was marked phenotypic variation. Cognitive impairment, psychiatric features and organic personality change occurred in over half the cases, and more than one-third had seizures. Orofaciolingual involuntary movements and pseudobulbar disturbance commonly caused dysphagia and dysarthria that was sometimes severe, but biting of the lips or tongue was rarely seen. Chorea was seen in almost all symptomatic cases but dystonia, tics, involuntary vocalizations and akinetic-rigid features also occurred. Two cases had no movement disorder at all. Computerized tomography often demonstrated cerebral atrophy. Caudate atrophy was seen less commonly, and nonspecific focal and symmetric signal abnormalities from the caudate or lentiform nuclei were seen by magnetic resonance imaging in 3 out of 4 cases. Depression or absence of tendon reflexes was noted in 13 cases and neurophysiological abnormalities often indicated an axonal neuropathy. Sural nerve biopsies from 3 cases showed evidence of a chronic axonal neuropathy with prominent regenerative activity, predominantly affecting the large diameter myelinated fibres. Serum creatine kinase activity was increased in 11 cases but without clinical evidence of a myopathy. Postmortem neuropathological examination in 1 case revealed extensive neuronal loss and gliosis affecting the corpus striatum, pallidum, and the substantia nigra, especially the pars reticulata. The cerebral cortex appeared spared and the spinal cord showed no evidence of anterior horn cell loss. Two examples of the McLeod phenotype, an X-linked abnormality of expression of Kell blood group antigens, were identified in a single family and included 1 female. The genetics of neuroacanthocytosis are unclear and probably heterogeneous, but the available pedigree data and the association with the McLeod phenotype suggest that there may be a locus for this disorder on the short arm of the X chromosome.
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PMID:Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases. 199 79

Acanthocytes have a distinct morphology and are not normally found in peripheral blood. They occur in association with at least three neurological syndromes. In abetalipoproteinaemia, a progressive spinocerebellar ataxia and retinopathy occurs secondary to malabsorption of vitamin E. Cases with chorea are often familial, with orofacial dyskinesia and an axonal neuropathy causing areflexia and muscle wasting. Areflexia and a subclinical myopathy also occur in the McLeod syndrome, in which there is abnormal expression of Kell blood group antigens. The exact mechanism of acanthocytosis in each disorder remains uncertain: passive changes in membrane lipids, surface receptor/ligand interactions, and a primary membrane defect are among the possibilities.
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PMID:Acanthocytosis and neurological impairment--a review. 268 30

McLeod syndrome is an Xp21-linked Kell blood group variant due to lack of erythrocyte protein Kx with associated RBC membrane dysfunction such as acanthocytosis. A man with this syndrome developed chorea and slight neuropsychological impairment. He had caudate atrophy on cerebral imaging and reduced striatal dopamine D2-receptor binding on single-photon emission computed tomography. Since Xp21 was partly deleted in the patient, the missing gene product (possibly Kx) may be essential for the integrity of the striatum.
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PMID:Cerebral involvement in McLeod syndrome. 829 45

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration and unusual red-cell morphology (acanthocytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (theta = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.
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PMID:Chorea-acanthocytosis: genetic linkage to chromosome 9q21. 938 1

A 52-year-old man was admitted to our hospital in 1997 because of high serum creatine kinase (CK) level. Neurologic findings revealed chorea on the trunk and extremities, mild weakness of proximal muscles, and absence of deep tendon reflexes in four extremities. Serum CK was elevated to 3,494 U/l (normal, below 235). A peripheral blood smear showed acanthocytes in approximately 1% of the red blood cells (RBCs). Very weak expression of the Kell antigens (K2, K4, K5, and K7) on his RBCs led us to make a final diagnosis of McLeod syndrome. Muscle biopsy from the left biceps showed increased variability in fiber diameter, a few regenerating fibers, scattered fibers with internal nuclei, and mild fiber type grouping. Immunohistochemical analyses of dystrophin. merosin, and adhalin were normal. Although McLeod syndrome is a rare X-linked recessive disorder, it is clinically important for differential diagnosis of chorea acanthocytosis and hyperCKemia.
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PMID:[A case of McLeod syndrome]. 1020 74

McLeod syndrome is a rare X-linked hematologic and neuromuscular disorder manifested by chorea, myopathy, cardiomyopathy, areflexia, hyperCKemia, and acanthocytosis. Only four mutations have been reported in the gene responsible for McLeod syndrome. We report a novel gene mutation in a Japanese family. Direct sequencing of the PCR-amplified genomic DNA revealed the mutation was a single C-nucleotide insertion at codon 151 in exon 2 of the XK gene, which resulted in a 3'-frameshift. Study of family members revealed that the patient's mother was a manifesting carrier heterozygous for this mutation.
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PMID:A novel mutation of the McLeod syndrome gene in a Japanese family. 1093 May 99

We report a patient of chorea-acanthocytosis (CA), presenting with dilated cardiomyopathy and myopathy. The patient, 40-year-old male, was seen in our clinic because of progressive gait disturbance. Neurologically, he had chorea, tic, dystonia, diminished tendon reflexes and mild muscular atrophy and weakness. Serum creatine kinase level was elevated to 5.514 IU/l, MRI study showed atrophy of the putamen and caudate nucleus. Peripheral nerve involvement was confirmed pathologically and electrophysiologically. Acanthocytosis was found after repeated blood examinations. Furthermore, he had dilated cardiomyopathy on echocardiogram and cardiac muscle biopsy, and his muscle biopsy taken from gastrocnemius indicated myopathic changes with fiber necrosis. From these clinical and laboratory data, he was suspected to have McLeod syndrome (McS). However, he had normal expression of Kell antigens, and direct sequence of XK gene from genomic DNA sample showed no mutations. Accordingly, he was diagnosed as having CA. As CA shares the similar clinical and laboratory features with McS except Kell antigens, the evaluation of Kell blood system is crucial for differential diagnosis. As seen in our patient, blood sampling should be repeated for identification of acanthocytosis, because the finding is not always clearly present.
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PMID:[A case of chorea-acanthocytosis with dilated cardiomyopathy and myopathy]. 1121 3

McLeod syndrome is a distinct form of neuroacanthocytosis. Its defining feature is the depression of erythrocyte Kell antigens. The underlying X chromosomal mutations cause a dysfunction of an erythrocyte membrane protein Kx. A choreatic movement disorder with caudate atrophy in CT and MRI has been reported in McLeod syndrome later in the course of the disease. Positron emission tomography with 18F-deoxyglucose (FDG) was performed in two unrelated affected men. In the older patient, progressive chorea was seen from the 5th decade. In the second patient there were no signs of a movement disorder at the age of 28. Positron emission tomography disclosed a reduction of the striatal FDG uptake in both patients, with accentuation in patient 1. Frontal lobe metabolism was not affected. Basal ganglia dysfunction with early impairment of striatal glucose metabolism thus seems obligatory for McLeod syndrome, as found in other forms of chorea with or without acanthocytosis.
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PMID:Reduction of striatal glucose metabolism in McLeod choreoacanthocytosis. 1125 78

The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2-fluoro-2-deoxy-glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X-linked trait should be examined for acanthocytosis and Kell/Kx blood group serology.
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PMID:McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. 1126 14

Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an autosomal recessive condition, vitamin E deficiency results in a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa. Neuroacanthocytosis is also probably an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysarthria, areflexia, seizures and dementia. McLeod syndrome is an X-linked recessive disorder usually presenting in males as a benign myopathy with areflexia, in association with a particular abnormality of expression of Kell blood group antigens. However, occasionally the neurological features are more severe and indistinguishable from those of neuroacanthocytosis. Recent advances in molecular genetics may assist better understanding of the disease mechanisms and the search for more effective treatments.
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PMID:Acanthocytosis and neurological disorders. 1128 40


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