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 28-year-old man developed slowly progressive dysarthria and gait disturbance over 7 years. Neurological examination revealed marked ataxia of articulation and gait, mild ataxia and spasticity of all four limbs without intellectual, visual, auditory, sensory or sphincter dysfunction. No physical signs of adrenal hypofunction were found. However, analysis of fatty acid of plasma sphingomyelin showed an increase in very long chain fatty acids, compatible with the diagnosis of adrenoleukodystrophy. Computed tomography disclosed marked atrophy of the cerebellum and pons, and bilateral low-density lesions in the deep while matter of the cerebellum. Magnetic resonance imaging showed these lesions more clearly, as well as other lesions in the middle and superior cerebellar peduncles, despite the absence of cerebral white matter involvement at the time of presentation. This is a rare case of adrenoleukodystrophy presenting as spinocerebellar degeneration and showing marked atrophy and several parenchymatous lesions of the cerebellum and brain stem.
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PMID:Ataxic variant of adrenoleukodystrophy: MRI and CT findings. 151 6

Adrenoleukodystrophy, an X-linked recessive disorder characterized by progressive demyelination of the central nervous system and adrenal insufficiency, usually manifests at 4-8 years of age. We report a 20-month-old male who presented with the sudden onset of status epilepticus and cortical blindness; initially, he had complete resolution of these findings, but experienced a relapse 3 months later. The initial computed tomographic scans depicted cerebral edema and possible "watershed infarcts:" however, over the next 2 weeks before discharge from the hospital, the cortical blindness and ataxia both resolved. During the next 2 months, he exhibited no symptoms: he had no seizures and his neurologic examinations were normal. Three months after the initial hospitalization, he developed what the mother believed was "a weakness on his right side." Magnetic resonance imaging confirmed severe white matter disease. Adrenoleukodystrophy was clinically suspected and an assay of plasma levels confirmed an elevation of C26 long-chain saturated fatty acid levels. After the patient's diagnosis of adrenoleukodystrophy was confirmed, long-chain fatty acid levels were obtained on his 5-year-old brother and his mother. This child had the earliest known onset of X-linked adrenoleukodystrophy.
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PMID:Variable phenotypes in a family kindred with adrenoleukodystrophy. 202 94

A family with adrenoleukodystrophy and clinical manifestations of spinocerebellar degeneration was studied. Two adult male first cousins showed progressive limb and truncal ataxia, slurred speech and spasticity of the extremities. Brain CT scans demonstrated atrophy of the pons and cerebellum, in both cases. Very long chain fatty acids in plasma and erythrocyte membranes were elevated in the affected patients and intermediately increased in an aunt and the mother of one patient, thereby indicating homozygotes and carriers of adrenoleukodystrophy, respectively. This unusual type of adrenoleukodystrophy seems to be transmitted as an X-linked recessive trait.
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PMID:Familial spinocerebellar degeneration as an expression of adrenoleukodystrophy. 346 5

A male patient was suspected as olivo-ponto-cerebellar atrophy from the clinical and computed tomographic features at 34 years of age. Afterwards, his dysarthria and limb ataxia were slowly and steadily worsened. He was finally bed-ridden and unresponsive, and died of hyperpyrexia and general wasting at 37 years of age. It was noted that laboratory investigation gave lower values of urinary 17-ketosteroids and 17-hydroxycorticosteroids in comparison with those of normal subjects. Pathological investigation in autopsy showed that he had pathological features consistent with adrenoleukodystrophy accompanying the olivo-ponto-cerebellar atrophy; diffuse demyelination in the cerebrocerebellear white matter, distorted architecture and cytoplasmic striations in the adrenal cortex, and in addition, a pseudosystemic degeneration of the olivo-ponto-cerebellar system and subcortical gray matter.
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PMID:An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: I. Clinical and pathological studies. 347 76

X-linked adrenomyeloneuropathy (AMN) is a phenotypic variant of adrenoleukodystrophy (ADL) presenting in early adult life with progressive ataxia and spasticity, and on occasion with adrenal insufficiency. We describe a 26-year-old Chinese man with a 2-year history of gait difficulty due to spasticity, absent pattern shift visual evoked (VER) responses and posterior white matter lesions on T2 weighted brain magnetic resonance images. His parents are clinically normal and his 24-year-old brother has hyperreflexia in the legs but normal VER latencies. The patient's ACTH levels were elevated and the serum cortisol did not rise with either Synacthen or corticotropin releasing hormone. Assay of his plasma confirmed elevation of very long chain fatty acids (VLCFA) consistent with a defect in peroxisomal VLCFA metabolism. This is the first local report of a patient with AMN.
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PMID:An index case of adrenomyeloneuropathy in a Chinese man. 776 96

A 36 year old male patient with adrenomyeloneuropathy (AMN) developed progressive spastic paraparesis and sensory ataxia from the age of 18. Biochemical studies showed increased plasma concentrations of saturated very long chain fatty acids (VLCFAs), subclinical evidence of adrenal insufficiency, and primary hypogonadism. Three female family members had increased plasma concentrations of VLCFAs, suggesting carrier status of adrenoleukodystrophy (ALD). Molecular genetic analysis detected a missense point mutation (C1930T) in exon 6 within the ALD gene, which predicts substitution of an amino acid (Ser515Phe) that is conserved between the deduced amino acid sequence of the peroxisomal membrane protein PMP70 and ALD protein. Detection of this point mutation allows diagnosis of ALD or AMN, identification of heterozygotes, and prenatal diagnosis of ALD.
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PMID:A missense point mutation (Ser515Phe) in the adrenoleukodystrophy gene in a family with adrenomyeloneuropathy: a clinical, biochemical, and genetic study. 787 58

Over the past few years, molecular neurogenetics has developed into one of the most promising and active research fields. The new discipline applies modern molecular genetic techniques to the investigation of classical neurological disorders. In the following article, a definition of neurogenetic disease is introduced, the molecular basis of four groups of neurogenetic disorders is described and recent diagnostic developments are presented. The first group of diseases is caused by trinucleotide expansions. "Expanding" trinucleotide repeats were not known to occur in any species until about three years ago. Today, disorders such as Huntington's disease, spinocerebellar ataxia type 1, fragile X mental retardation, spinobulbar muscular atrophy and myotonic dystrophy are all known to be caused by the expansion of trinucleotides. The second group is characterized by chromosomal deletions or uniparental disomies. Lissencephaly and the Miller-Dieker syndrome, Prader-Willi and Angelman syndromes and Duchenne and Becker muscular dystrophies belong to this category. The third group includes those neurogenetic disorders that are mainly caused by point mutations such as the X-linked leukodystrophies, including Pelizaeus-Merzbacher disease and adrenoleukodystrophy, Charcot-Marie-Tooth syndrome type 1, familial forms of amyotrophic lateral sclerosis, several types of craniosynostoses and some CNS tumor syndromes. Finally, Alzheimer's and Parkinson's disease are discussed as representatives of group four, i.e. genetically heterogeneous neurological disorders.
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PMID:Molecular basis and diagnosis of neurogenetic disorders. 796 63

We report on monozygotic twins with different clinical phenotypes of X-linked adrenoleukodystrophy. At the age of 10 years both boys were neurologically asymptomatic. The first cranial magnetic resonance examination showed normal findings in the first twin and parietooccipital demyelination in the second. The latter developed behavioral problems 9 months later, followed by visual impairment and gait ataxia. His cranial magnetic resonance image at the age of 11 years showed progressive demyelination. In contrast, neurological status and magnetic resonance images remained normal in the first twin. The same point mutation in exon 8 of the adrenoleukodystrophy gene (C2203T) was detected in both boys. All genotype examinations were consistent with the diagnosis of monozygotic twins, suggesting that some nongenetic factors may be important for different adrenoleukodystrophy phenotypes.
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PMID:Cerebral adrenoleukodystrophy (ALD) in only one of monozygotic twins with an identical ALD genotype. 877 11

X-linked adrenoleukodystrophy (ALD) usually presents in childhood as severe cerebral demyelination accompanied by axonal loss or in adults as a progressive spinal cord syndrome (adrenomyeloneuropathy). Rarely, patients present with adult onset spinocerebellar ataxia. We performed mutation analysis in a family with several members who had this rare phenotype and identified a single nucleotide deletion in exon 2 of the ALD gene. This is the first mutation analysis to be reported in this unusual phenotypic variant of ALD and the first deletion to be reported in exon 2.
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PMID:A novel point mutation in X-linked adrenoleukodystrophy presenting as a spinocerebellar degeneration. 1031 88

The phenotypic variability in X-linked adrenoleukodystrophy (X-ALD) can be wide and varied. Rarely, it can present with clinical signs of spinocerebellar degeneration. There are very few reported cases of selective predominant white matter disease of the cerebellum in these patients. We report a patient with a rare variant of adult onset ALD who was previously diagnosed as spinocerebellar ataxia. He was a 24-year-old male who had delayed developmental milestones, developed signs of spinocerebellar degeneration (SCD) after 10 years of Addison's disease. Serial Magnetic Resonance Imaging (MRI), revealed cerebellar and pontine white matter disease but sparing the cerebral cortex and supratentorial white matter. His diagnosis of X-ALD was subsequently confirmed by the elevated serum very long chain fatty acids. This patient illustrates the unusual clinical presentation and imaging features of X-ALD and the importance of considering X-ALD in the clinical context of spinocerebellar degeneration. Early recognition of this rare variant would allow proper genetic counselling and institution of dietary therapy and/or bone marrow transplantation.
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PMID:X-linked adrenoleukodystrophy: spinocerebellar variant. 1046 13


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