Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A systematic study of plasma lipids and lipoproteins was carried out in 11 cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using 11 healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.
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PMID:Plasma lipids and lipoproteins in Friedreich's ataxia and familial spastic ataxia--evidence for an abnormal composition of high density lipoproteins. 20 32

A six-year-old Japanese boy had ataxia, mental retardation, peripheral neuropathy, proximal myopathy, hearing loss, retinitis pigmentosa and deficiencies in apolipoprotein AI, B, CII and CIII. His clinical features except for hearing loss resembled those of abetalipoproteinaemia or symptomatic hypobetalipoproteinaemia, but his apolipoprotein abnormalities were distinct from these disorders. He had apolipoprotein B-100 with a normal molecular weight. Although most of his neurological manifestations were compatible with those of vitamin E deficiency, their early onset and the presence of hearing loss was unusual for that condition. There has been slight deterioration of ataxia during two years follow-up despite high-dose vitamin E supplementation. Other abnormalities in lipid metabolism might be associated with the neurological damage in this case.
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PMID:A variant form of hypobetalipoproteinaemia associated with ataxia, hearing loss and retinitis pigmentosa. 795 7

We report a Canadian kindred with a novel mutation in the apolipoprotein (apo) A-I gene causing analphalipoproteinemia. The 34-yr-old proband, product of a consanguineous marriage, had bilateral retinopathy, bilateral cataracts, spinocerebellar ataxia, and tendon xanthomata. High density lipoprotein cholesterol (HDL-C) was < 0.1 mM and apoA-I was undetectable. Genomic DNA sequencing of the proband's apoA-I gene identified a nonsense mutation at codon [-2], which we designate as Q[-2]X. This mutation causes a loss of endonuclease digestion sites for both BbvI and Fnu4HI. Genotyping identified four additional homozygotes, four heterozygotes, and two unaffected subjects among the first-degree relatives. Q[-2]X homozygosity causes a selective failure to produce any portion of mature apoA-I, resulting in very low plasma level of HDL. Heterozygosity results in approximately half-normal apoA-I and HDL. Gradient gel electrophoresis and differential electroimmunodiffusion assay revealed that the HDL particles of the homozygotes had peak Stokes diameter of 7.9 nm and contained apoA-II without apoA-I (Lp-AII). Heterozygotes had an additional fraction of HDL3-like particles. Two of the proband's affected sisters had documented premature coronary heart disease. This kindred, the third reported apoA-I gene mutation causing isolated complete apoA-I deficiency, appears to be at significantly increased risk for atherosclerosis.
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PMID:Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. 828 91

Genetic deficiencies of plasma high-density lipoprotein cholesterol are associated variably with diseases of the eyes and nervous system. We ascertained a proband with undetectable plasma HDL-cholesterol due to homozygosity for a DNA mutation, APOA1 Q[-2]X, which encodes premature termination of translation of apolipoprotein in HDL. This person had a unique retinopathy, ataxia, and electrophysiologic abnormalities suggesting multifocal central nervous system deficits. Other gene carriers in this family had similar neurologic features, but only the proband had the retinopathy. The presence of retinopathy and neuropathy in affected family members was highly variable. This heterogeneity might results from time-dependent interactions with other genetic or environmental factors.
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PMID:Case report: retinopathy and neuropathy associated with complete apolipoprotein A-I deficiency. 868 27

Retinoic acid receptor-related Orphan Receptor alpha (RORalpha) is a member of the nuclear hormone receptor superfamily. RORalpha has long been considered as a constitutive activator of transcription in the absence of exogenous ligand; however, cholesterol has recently been identified as a natural ligand of RORalpha. The spontaneous staggerer (sg/sg) mutation is a deletion in the Rora gene that prevents the translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. The homozygous Rora(sg/sg) mutant mouse, of which the most obvious phenotype is ataxia associated with cerebellar degeneration, also displays a variety of other phenotypes, including several vascular ones; in particular, dysfunction of smooth muscle cells and enhanced susceptibility to atherosclerosis. Moreover, RORalpha appears to participate in the regulation of plasma cholesterol levels, and has been shown to positively regulate apolipoprotein (apo)A-I and apoC-III gene expression. Yet its activity is regulated by cholesterol itself, making RORalpha an intracellular cholesterol target.
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PMID:The "CholesteROR" protective pathway in the vascular system. 1475 13