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)

Biotinidase deficiency is the primary defect in most individuals with late-onset multiple carboxylase deficiency. We have reviewed the presenting clinical features of 31 children with the disorder. Seizures, either alone or with other neurological or cutaneous findings, are the most frequent initial symptom observed. Other neurological symptoms, such as hypotonia, ataxia, hearing loss, optic atrophy, and developmental delay, are seen, in addition to skin rash and alopecia. The disorder is also characterized by ketolactic acidosis and organic aciduria. Biotinidase activity may be diagnosed using a simple, rapid, semiquantitative colorimetric procedure. Samples of whole blood spotted on the same filter paper used by most states to screen for phenylketonuria and other inborn errors of metabolism may be sent to an appropriate reference laboratory. None of the common anticonvulsants or sedatives used to treat newborns and children interfere with the test. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.
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PMID:Biotinidase deficiency: initial clinical features and rapid diagnosis. 407 53

Heterozygotes of autosomal-recessive diseases can often be recognized by special heterozygote tests, since enzyme activities are normally reduced in comparison with the normal homozygote state. In Drosophila, the majority of recessive lethal mutations shows a reduction of fitness in heterozygotes, whereas in a strong minority fitness of heterozygotes is increased. This review will be devoted to a consideration of the extent to which heterozygotes for a wide variety of nominally recessive diseases are subject either to an increased liability for common diseases or slight shifts of behavioral characteristics. The available evidence has been collected and will be discussed in three steps: Most studies are available for phenylketonuria. For this group of diseases, a slight reduction of average--especially verbal--I.Q. in heterozygotes has been reported together with signs of a slightly increased cerebral irritability, a possible slight increase of risk for mental disease, and an increase of blood phenylalanine levels in stress situations. The PKU example is used to discuss methodological problems involved in such studies. Other conditions for which relevant deviations in heterozygotes are possible or even likely include among others lipid storage diseases, microcephaly, myoclonus epilepsy, Wilson's disease, galaktokinase deficiency, homocystinuria, recessive myotonia and ataxia- teleangiectasia (increased cancer risk). Since heterozygotes for autosomal recessive diseases are common, it is possible that an appreciable fraction of "multifactorial" genetic liabilities for common, "constitutional" or mental disease might simply be due to heterozygosity for genes whose homozygous affects are already well known. By the same token, much of the "normal" genetic variability influencing cognitive performance (I.Q.)--especially in the lower range--and personality characteristics could also be caused by recessive genes in the heterozygous state.
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PMID:Clinical consequences of heterozygosity for autosomal-recessive diseases. 637 70

Reduction of intelligence should be differentiated from interference with the use of intelligence by such non-intellective factors as partial deafness and emotional disturbance. The parents of a retarded child want an assessment, a prediction of the eventual achievement level, and a causal explanation if possible. There are varying degrees of knowledge of causation, from recognition of reduced intelligence only, to an understanding of the mechanism of causation in considerable detail from primary cause to ultimate consequence, as in phenylketonuria or isoimmunization. A diagnosis should be as complete as possible, using available modern techniques of investigation, such as chromatography and cytogenetic studies.AMONG THE RECENTLY DESCRIBED SYNDROMES ASSOCIATED WITH MENTAL RETARDATION ARE: (1) spastic paralysis and congenital ichthyosis; (2) Rud's syndrome; (3) deaf-mutism, infantilism, ataxia and a disturbance of hormone metabolism; and (5) sex-linked deaf-mutism.
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PMID:MENTAL RETARDATION: METHODS OF DIAGNOSIS AND SOME RECENTLY DESCRIBED SYNDROMES. 1408 87

Metabolic diseases of the nervous system vary considerably in their clinical and pathological aspects. In neurological presentations of these disorders dominate mental retardation and epileptic syndrome. We have studied 27 patients of age from 3 months to 3 years: PKU -- 15 cases; homocystinuria -- 4; hyper-prolinemia -- 1; methylmalonic acidemia -- 5 and combined disorders -- 2. Epileptic syndrome was revealed in 21 patients, mental retardation in 1, spasticity in 5 and ataxia in 1 patient. Epileptic syndrome was presented with generalized seizures (grand mal -- 6 cases, myoclonic absences -- 13 cases) and partial seizures (simple motor -- 2 cases). Investigations did not found reliable correlations between certain forms of enzymophaties and EEG patterns. Patients were treated by pathogenic (dietary management with protein-modified diet and vitamin therapy) and symptomatic (anticonvulsants) treatment. We have achieved the positive therapeutic effect by pathogenic and anticonvulsive treatment in 11 patients. All these patients were from the first group (1-3 year). The best outcome was observed in the cases of the early diagnosed PKU. The most severe mental retardation and resistant epilepsy were revealed in patients with combined disorders of metabolism and vitamin-non-responsive forms of MMA and HCS.
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PMID:[Peculiarities of epileptic syndrome in children with metabolic disorders of nervous system]. 1636 68

We describe three unrelated individuals, two males (ages 35 and 9) and a female (age 8) presenting with late diagnosed phenylketonuria (PKU) and autistic behavior, all showing poor adhesion to the dietary treatment resulting in high plasmatic phenylalanine levels, particularly in the oldest subject. Clinical findings included hair hypopigmentation, microcephaly, severe mental retardation with absent development of verbal language and autistic symptoms in all three patients, whereas variable neurological signs such as seizures, spasticity, ataxia, aggressivity, and hyperactivity were individually found. Homozygosity for the IVS10nt11g/a (IVS10nt546) was found in all. This is the first report of molecular findings in subjects with PKU also presenting with autistic features. The authors discuss if this mutation is particularly involved in the association of autistic symptoms in untreated PKU individuals.
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PMID:Genotype and natural history in unrelated individuals with phenylketonuria and autistic behavior. 1760 14

Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been identified and characterized in detail within recent decades, with promising therapeutic options. Neuroimaging is becoming increasingly utilized in earlier stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so as to monitor disease progress and treatment response. This review attempts to summarize in a concise fashion the neuroimaging findings of various CIEMs that may present in adulthood, as well as those that may persist into adulthood, whether because of beneficial therapy or a delay in diagnosis. Notably, some of these disorders have neuroimaging findings that differ from their classic infantile or early childhood forms, whereas others are identical to their early pediatric forms. The focus of this review is their appearance on routine magnetic resonance imaging sequences, with some basic attention to the findings of such CIEMs on specialized neuroimaging, based on recent or preliminary research. The general classes of disorders covered in this complex review are: peroxisomal disorders (adrenoleukodystrophy), lysosomal storage disorders (including metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry, Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases), mitochondrial disorders (including mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers, Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3-methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia, proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric acidurias), cytoskeletal or transporter molecule defects (including Alexander or fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher, Wilson, and Huntington diseases), and several neurodegenerative disorders of brain iron accumulation. Additionally, an arbitrary "miscellaneous" category of 5 recognizable disorders that may present in or persist into adulthood is summarized, which include megalencephalic leukoencephalopathy with subcortical cysts (megancephalic leukoencephalopathy with subcortical cysts or van der Knaap disease), polymerase-III gene defect ("4H syndrome"), childhood ataxia with central nervous system hypomyelination ("vanishing white matter disease"), striopallidodentate calcinosis ("Fahr disease"), and Cockayne syndrome.
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PMID:Congenital genetic inborn errors of metabolism presenting as an adult or persisting into adulthood: neuroimaging in the more common or recognizable disorders. 2474 91