Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.12 (biotinidase)
 392 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Late-onset multiple carboxylase deficiency depends on biotinidase deficiency and is inherited as an autosomal recessive trait. Lipoamidase deficiency in humans has not been previously reported, using the natural substrate lipoyllysine for lipoamidase. In this report we describe a simultaneous decrease in both lipoamidase and biotinidase activity in serum from a 21 month-old boy with a profound biotinidase deficiency. Lipoamidase activity in human serum was determined with both lipoyllysine (epsilon-N-(D,L-lipoyl)-L-lysine) and N-D,L-lipoyl-p-aminobenzoate as substrates. Biotinidase activity was determined with both biocytin (epsilon-N-(D-biotinyl-L-lysine) and N-D-biotinyl-p-aminobenzoate as substrates. Our findings indicate that lipoamidase activity and biotinidase activity in human serim are due to the same enzyme, but a "residual activity" was usually found when N-D,L-lipoyl-p-aminobenzoate was used as a substrate. Compared with the activity in control serum, this "residual activity" was little affected by inhibition with biocytin, indicating that a small fraction of a modified biotinidase probably exists.
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PMID:Lipoamidase and biotinidase deficiency: evidence that lipoamidase and biotinidase are the same enzyme in human serum. 159 76

Purified human serum biotinidase exhibited amino-exo-peptidase activity. Enkephalins and dynorphin A (less than 10-mer) seemed to be the most appropriate substrates among various physiological peptides in terms of the kcat/Km values. Similar kcat/Km values were obtained for both biocytin (biotinyllysine) and these opioid-neuropeptides. Neuro-oligo-peptides ranging from 2-mer to 18-mer were hydrolyzed. The presence of amino group at the carboxyl terminal position increased the kcat/Km value by decreasing the Km value. The results of inhibition studies using various kinds of antibiotic inhibitors, metals, and chelating agents indicated that enkephalin hydrolysis was mediated by the peptide-hydrolyzing center probably containing Zn ions. This aminopeptidase activity was uniquely inhibited by a vitamin of biocytin. The reason for the high content of biotinidase activity in serum may be related to the binary function of this enzyme; i.e., biocytin hydrolyzing amidase and enkephalin hydrolyzing aminopeptidase functions.
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PMID:Enkephalin hydrolysis by human serum biotinidase. 167 65

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

The biochemical and immunological characterization of biotinidase was performed in sera from 100 normal individuals, 68 children with profound biotinidase deficiency (less than 10% of mean normal activity) who were identified symptomatically and by newborn screening, and 63 of their parents. On isoelectric focusing, serum enzyme from normal individuals exhibits extensive microheterogeneity, consisting of at least four major and five minor isoforms at pH 4.15-4.35. Patients with profound biotinidase deficiency can be classified into at least nine distinct biochemical phenotypes, on the basis of (a) the presence or absence of cross-reacting material (CRM) to biotinidase, (b) the number of isoforms, and (c) the distribution frequency of the isoforms. None of the patients with CRM had an abnormal Km of the substrate for the enzyme. All of the parents had normal isoform patterns. The mean activities, CRM concentrations, and specific activities were not significantly different between parents of CRM-positive children and parents of CRM-negative children. There is no relationship between either the age at onset or the severity of symptoms and the isoform patterns or CRM status of the symptomatic children. The isoform patterns of children identified by newborn screening are not different from those of symptomatic children.
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PMID:Biochemical and immunological characterization of serum biotinidase in profound biotinidase deficiency. 172 84

A patient with a newly recognised variant of biotinidase deficiency presented with acute loss of vision at the age of 10 years. Progressive bilateral optic neuropathy, spastic paraparesis, and a predominantly motor type neuropathy developed over the next five years. Metabolic investigations revealed biotin depletion causing multiple carboxylase deficiency. The basic defect was a biotin recycling disorder due to a mutant biotinidase with residual activity of 4.4% assayed routinely. Biocytin excretion in urine was only slightly increased. Further investigations on plasma biotinidase revealed biphasic kinetics with two different reduced values for maximum reaction velocity (Vmax) and two for the Michaelis constant (Km), one being almost normal and the other considerably raised. In contrast to this patient, two age matched children with partial biotinidase deficiency (2.8% and 2.9% of normal), but with a normal Km for biocytin, remained asymptomatic. After six months of oral substitution with 10 mg biotin per day the coecocentral and peripheral scotomata regressed, the pyramidal signs in the lower limbs disappeared, and further progression of the motor neuropathy arrested. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease, should include biotinidase deficiency.
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PMID:A biotinidase Km variant causing late onset bilateral optic neuropathy. 173 23

Governmental officials as well as medical scientists in Taiwan have worked hard in recent years to develop and to implement various measures, such as prenatal diagnosis and neonatal screening, to lower the incidence of hereditary diseases and mental retardation in the population. An inquiry into the possibility of devising a chromosomal and biochemical screening program and to apply it routinely to all the mentally retarded school children island-wide was the major aim of the present study. A collection of 1,614 blood samples was screened for phenylketonuria (PKU), galactosemia, homocystinuria, biotinidase deficiency, and congenital hypothyroidism. The IQ of these children ranged from 50-75 (1,397 children, moderate group) to less than 50 (217 children, severe group). Six cases of PKU (one tetrahydrobiopterin deficient and five classical) and three cases of thyroid dysfunction were found. The overall incidence of these two diseases was 0.56%. Of the 1,614 blood samples, 1,323 were cultured and karyotyped successfully. One hundred and twenty-five of them had chromosome abnormalities. The majority (64 out of 125) were trisomy 21. A remarkable difference in the percentage of mentally retarded children with chromosome abnormalities was observed between the moderate (7.87%) and severe (17.51%) retarded.
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PMID:Chromosomal and biochemical screening on mentally retarded school children in Taiwan. 175 40

This article reviews current knowledge concerning the dermatologic manifestations of biotin deficiency. Biotin is a water-soluble vitamin that acts as an essential cofactor for four carboxylases, each of which catalyzes an essential step in intermediary metabolism. For example, acetyl-CoA carboxylase catalyzes the rate-limiting step in fatty acid elongation. In infants, children, and adults, deficiency of biotin causes alopecia and a characteristic scaly, erythematous dermatitis distributed around body orifices. The rash closely resembles that of zinc deficiency. Candida albicans often can be cultured from the skin lesions. Biotinidase deficiency, an inborn error, causes biotin deficiency, probably as a consequence of unpaired intestinal absorption, cellular salvage, and renal reclamation of biotin; biotinidase deficiency causes dermatologic manifestations similar to biotin deficiency. There is evidence that impaired fatty acid metabolism secondary to reduced activities of the biotin-dependent carboxylases (especially acetyl-CoA carboxylase) plays an etiologic role in the dermatologic manifestations of biotin deficiency. Candida infections secondary to impaired immune function might also contribute to the dermatitis of biotin deficiency.
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PMID:Skin manifestations of biotin deficiency. 176 57

A radioassay for determining biotinidase activity in human serum was developed, using N-[beta-(4-OH-3-125I-phenyl)ethyl]-biotinamide in combination with biocytin as the substrate, avidin as a binding protein, and polyethylene glycol as a separation reagent. The gamma-emitting 125I-biotinamide (= tracer) was synthesized by coupling (pH 8.5, 20-22 degrees C, 90 min) N-hydroxysuccinimidobiotin to 125I-tyramine. Using polyethylene glycol as a separation reagent, it was possible to eliminate several problems that were encountered when other separation reagents were used. Biotinidase activity was evaluated following the cleavage of the 125I-biotinamide and expressed in fmol of tracer cleaved.min-1.ml-1 in the presence of 9 nmol of biocytin. Under the conditions used, the time response of the assay was linear up to 3 h. The method is simple to perform, more sensitive than the previously described methods, and reproducible (intra- and interassay CVs of 4.9 and 10.2%, respectively) and allows the simultaneous handling of more than 100 samples in less than 3 h.
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PMID:Biotinidase radioassay using an 125I-biotin derivative, avidin, and polyethylene glycol reagents. 177 89

Neonatal screening for biotinidase deficiency has been conducted in 14 countries since 1984. To 31 December 1990, 8,532,617 newborns were screened. One hundred and forty-two infants with biotinidase deficiency were identified; 76 infants with profound deficiency (less than 10% of mean normal serum activity) and 66 infants with partial deficiency (10-30% of mean normal activity). The estimated incidence of profound biotinidase deficiency is 1:112,271 (1:85,000 to 1:145,000; 95% confidence limits) and the incidence of partial deficiency is 1:129,282 (1:112,700 to 1:177,000). The incidence of combined profound and partial deficiency is 1:60,089 newborns (1:49,500 to 1:73,100). The estimated frequency of the allele for biotinidase deficiency is 0.004 and an estimated 1 in 123 individuals is heterozygous for the disorder.
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PMID:Worldwide survey of neonatal screening for biotinidase deficiency. 177 51

There are two types of multiple carboxylase deficiency, the neonatal form with holocarboxylase synthetase defect and the late-onset form with biotinidase deficiency. We report our preliminary experiences in screening for biotinidase deficiency. In total 43,493 infants were screened for the deficiency of the enzyme biotinidase; 0.14% false positive results that necessitated requests for second blood samples and two newborns with a biotinidase defect were identified during our pilot study. The definitive diagnosis required the demonstration of enzyme deficiency in serum. Both of the patients have residual biotinidase activity: 3.59% and 7.55%. These two newborns with biotinidase deficiency are treated with daily supplementation of free biotin. According to our preliminary results biotinidase deficiency satisfies all the criteria for incorporation into the national newborn mass screening.
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PMID:Neonatal screening for biotinidase deficiency in east-Hungary. 177 52


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