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)

To test the hypothesis that the frequency of biotinidase deficiency is greater in children with unexplained developmental delay or neurologic abnormalities than in the general population, we studied children seen at a large outpatient clinic over a four-year period who had one or more of these neurologic abnormalities and for whom no specific cause for their abnormalities could be found. The group totaled 274 children (163 boys; 111 girls) whose ages ranged from 2 weeks to 17 years. Characteristics were IQ/DQ, 30 to 70 in the 115 for whom scores were available; 41% had seizures; 15% had sensorineural hearing loss; 54% showed gross motor delay or ataxia; and 27% had decreased muscle tone. One patient with a classical clinical picture of biotinidase deficiency was diagnosed during the study period and was not included in the study. None of the patients with nonclassic findings had a deficiency of biotinidase activity. Our results suggest that biotinidase deficiency does not account for a large proportion of children with unexplained neurologic abnormalities or developmental delay. This does not negate the importance of biotinidase testing in children with clinical patterns specifically suggestive of the deficiency.
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PMID:Screening for biotinidase deficiency in children with unexplained neurologic or developmental abnormalities. 170 49

Biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency and an autosomal recessive disorder and characterized by seizures, ataxia, alopecia and skin rash. We describe a colorimetric semiquantitative method for screening for biotinidase activity from dried samples of whole blood spotted on filter papers. The administration of biotin to affected children can be a lifesaving procedure and can prevent irreversible neurologic damage.
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PMID:[Biotinidase deficiency--a progressive metabolic disease in children with seizures and ataxia]. 235 50

Ten patients with biotinidase deficiency were studied. Clinical findings at presentation varied with dermatological signs (dermatitis and alopecia), neurological abnormalities (fits, hypotonia, and ataxia), and recurrent infections being the most common features, although none of these occurred in every case. Biochemically the disease is characterised by metabolic acidosis and organic aciduria. Treatment with biotin results in pronounced, rapid, clinical and biochemical improvement, but some patients have residual neurological damage comprising neurosensory hearing loss, visual pathway defects, ataxia, and mental retardation. The cause of this permanent damage remains obscure and it is not clear if the early introduction of treatment will prevent it.
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PMID:Biotinidase deficiency: a survey of 10 cases. 319 50

Biotinidase deficiency leads to a biotin-deficient state, with cardinal symptoms of ataxia, alopecia, and skin rash presenting in infancy. Previous reports of head CTs in patients with biotinidase deficiency did not note basal ganglia calcifications. We report the first case of biotinidase deficiency with basal ganglia calcifications. There were no symptoms referable to basal ganglia dysfunction.
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PMID:Basal ganglia calcifications in a case of biotinidase deficiency. 339 84

Prominent neurological abnormalities, including myoclonus, seizures, ataxia, and hearing loss, have been noted in juvenile-onset biotin-responsive MCD. The underlying defect in many of these patients, who generally present in the first year of life, appears to be a deficiency of biotinidase. We have presented a young woman with adult-onset myoclonus, ataxia, hearing loss, seizures, hemianopia, and hemiparesis who responded to pharmacologic dosages of biotin. Although she displayed many of the clinical and biochemical features of juvenile-onset MCD, she did not have a biotinidase deficiency, and the underlying defect remains to be determined. Because of her response to biotin, we have advocated that other patients with unexplained myoclonus syndromes be evaluated for biotin-dependent carboxylase deficiencies and undergo a therapeutic trial with biotin.
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PMID:Biotin-responsive encephalopathy with myoclonus, ataxia, and seizures. 394 8

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

Biotinidase deficiency is the usual biochemical defect in biotin-responsive late-onset multiple carboxylase deficiency. We reviewed the clinical features of six patients with the enzyme deficiency and compared them with features described in the literature in children with late-onset MCD. In all of the reported probands, MCD was diagnosed because they had metabolic ketoacidosis and organic aciduria in addition to various neurologic and cutaneous symptoms, such as seizures, ataxia, skin rash, and alopecia. Although in several of our patients biotinidase deficiency was also diagnosed because they manifested a similar spectrum of findings, others never had ketoacidosis or organic aciduria. Thus the initial features of biotinidase deficiency usually include neurologic or cutaneous symptoms, whereas organic aciduria and MCD are delayed, secondary manifestations of the disease. These findings suggest that biotinidase deficiency should be considered in any infant or child with any of these neurologic or cutaneous findings, with or without ketoacidosis or organic aciduria. If the diagnosis cannot be excluded, such individuals should be given a therapeutic trial of pharmacologic doses of biotin.
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PMID:Phenotypic variation in biotinidase deficiency. 687 14

Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. Biochemically, these individuals exhibit findings consistent with a combined deficiency of the biotin-dependent carboxylases. We have found that the activity of the enzyme biotinidase is also deficient in the sera of five affected children (0 to 3% of mean control activity, 5.80 +/- 0.89 nmol X min-1 X ml-1 serum), and believe that it represents the primary biochemical defect in this disease. Biotinidase catalyzes the removal of biotin from the epsilon-amino group of lysine, through which biotin is covalently bound to the four known human carboxylases, thereby regenerating biotin for reutilization. The deficient activity in our patients was not due to an inhibitor, particularly biotin. It is also not a consequence of feedback control in affected individuals under treatment with pharmacologic doses of biotin. The biotinidase activities of the parents of those children who were available for study were intermediate between deficient and normal values (46% to 65% of mean normal activity). Children lacking biotinidase activity are unable to recycle biotin, and are thus entirely dependent upon exogenous biotin to prevent deficiency. Our findings indicate that the primary biochemical defect in late-onset multiple carboxylase deficiency is in biotinidase activity which is inherited as an autosomal recessive trait.
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PMID:Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. 688 21

Three patients with biotinidase deficiency are described. Two presented at eight weeks of age with anticonvulsant-resistant fits, developmental delay and hypotonia. Treatment has been effective. The third developed ataxia and alopecia at 14 months and died suddenly at 19 months of age. In all three cases the diagnosis was not considered quickly enough. Biotinidase deficiency is a treatable cause of severe neurological problems.
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PMID:Biotinidase deficiency: early neurological presentation. 805 Jun 27

Acquired biotin deficiency and the two known congenital disorders of biotin metabolism, biotinidase and holocarboxylase synthetase (HCS) deficiency, all lead to deficiency of the 4 biotin-dependent carboxylases, i.e. to multiple carboxylase deficiency (MCD). The underlying mechanism in HCS-deficiency, discovered in 1981, is decreased affinity of HCS for biotin impairing the formation of holocarboxylases at physiological biotin levels. In biotinidase deficiency, discovered in 1983, MCD results from progressive development of biotin-deficiency due to inability to liberate and recycle biotin which is lost in urine as biocytin. MCD leads to typical organic aciduria and severe life-threatening illness. Main symptoms and signs are feeding difficulties, neurologic abnormalities (hypotonia, impaired consciousness, seizures, ataxia) and cutaneous changes (rash, alopecia). However, the clinical presentation and age of onset are extremely variable, and organic aciduria may initially be absent in biotinidase deficiency. Therefore, the definitive diagnosis requires enzyme studies. MCD can be detected in lymphocytes obtained before treatment and biotinidase deficiency is confirmed or excluded by a colorimetric enzyme assay in plasma. Newborn screening for biotinidase deficiency has resulted in the detection of patients with partial deficiency (10-30% of mean normal activity) in addition to patients with profound deficiency (0-10%). Severe illness has been observed mainly in patients with O-activity or a Km-mutation, detection of which requires detailed investigation. HCS-deficiency has to be confirmed by enzyme assay in cultured cells. Both congenital disorders respond clinically and biochemically to oral biotin therapy. Whereas 10 mg/day or less is sufficient to treat profound biotinidase deficiency, the optimal biotin dose for patients with HCS-deficiency must be assessed individually. The prognosis of both disorders is good if biotin therapy is introduced early and continued throughout life. However, delayed commencement of therapy in biotinidase deficiency can result in irreversible neurological damage, and in HCS-deficiency a few patients have responded only partially even to massive biotin doses of up to 100 mg/day.
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PMID:Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. 935 Apr 81


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