The Experts below are selected from a list of 591 Experts worldwide ranked by ideXlab platform
Barry Wolf - One of the best experts on this subject based on the ideXlab platform.
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Biotinidase Deficiency should be considered in individuals thought to have multiple sclerosis and related disorders
Multiple sclerosis and related disorders, 2019Co-Authors: Barry WolfAbstract:Abstract Background Multiple sclerosis is a disorder of the central and peripheral nervous system of young and old adults that is characterized by muscle, coordination and vision abnormalities. Multiple sclerosis is likely due to numerous causes. Methods Recently, adolescents and adults with ophthalmological and or neurological findings have been diagnosed with Biotinidase Deficiency. These individuals have exhibited myelopathy, paresis and/or spastic diplegia/tetraplegia with or without optic neuropathy/vision loss. These older individuals with Biotinidase Deficiency were considered initially to have multiple sclerosis or similar disorders before they were determined to have Biotinidase Deficiency. Results If a symptomatic individual with Biotinidase Deficiency is treated with biotin early enough, the symptoms markedly improve or completely resolve, but if treatment is delayed, the symptoms may be irreversible. Conclusion Therefore, although Biotinidase Deficiency is rare relative to that of multiple sclerosis, the disorder should be included in the differential diagnosis of individuals thought to have multiple sclerosis or related disorders. Biotinidase Deficiency should be considered in individuals thought to have multiple sclerosis or related disorders.
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successful outcomes of older adolescents and adults with profound Biotinidase Deficiency identified by newborn screening
Genetics in Medicine, 2017Co-Authors: Barry WolfAbstract:We began screening newborns for Biotinidase Deficiency disorder in 1984, and now all states in the United States and many countries perform this screening. The purpose of this study was to determine the outcomes of older adolescent and adult individuals with the disorder identified by newborn screening. We located and surveyed, by questionnaire and telephone interviews, 44 individuals with profound Biotinidase Deficiency identified by newborn screening with a mean age of 23.1 years. All individuals had successfully completed high school, and many were attending or had completed college or graduate school. Compliance in using biotin has been excellent. Several individuals developed a variety of symptoms when they discontinued biotin for days or weeks. These features readily resolved when biotin was resumed. In addition, five treated women had nine uneventful pregnancies and deliveries. Newborn screening for profound Biotinidase Deficiency and early treatment with biotin result in excellent outcomes for older adolescents and adults with the disorder. In addition, mothers with profound Biotinidase Deficiency who were treated with biotin had pregnancies with good outcomes. These outcome results indicate that newborn screening for Biotinidase Deficiency is one of the most successful newborn screening programs. Genet Med 19 4, 396–402.
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irreversibility of symptoms with biotin therapy in an adult with profound Biotinidase Deficiency
JIMD reports, 2017Co-Authors: Patrick Ferreira, Alicia Chan, Barry WolfAbstract:We report a 36-year-old woman who exhibited progressive optic atrophy at 13 years old, then stroke-like episodes and spastic diplegia in her 20s. Biotinidase Deficiency was not readily considered in the differential diagnosis, and the definitive diagnosis was not made until pathological variants of the Biotinidase gene (BTD) were found by exome sequencing. Profound Biotinidase Deficiency was confirmed by enzyme analysis. Unfortunately, her symptoms did not resolve or improve with biotin treatment. Biotin therapy is essential for all individuals with profound Biotinidase Deficiency and for preventing further damage in those who already exhibit irreversible neurological damage. Newborn screening for the disorder would have avoided years of clinical symptoms that now appear to be irreversible with biotin treatment.
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Biotinidase Deficiency and our champagne legacy
Gene, 2016Co-Authors: Barry WolfAbstract:Biotinidase is the enzyme that is necessary for the recycling of the vitamin, biotin. Biotinidase Deficiency is an autosomal recessively inherited metabolic disorder. If untreated, individuals with Biotinidase Deficiency usually develop neurological and cutaneous symptoms that can result in coma or death. Symptomatic individuals can be markedly improved by treating them with pharmacological doses of biotin; however, some clinical features may be irreversible. Fortunately, essentially all symptoms can be prevented if treatment is initiated at birth or before the symptoms develop. Because of this, the disorder is currently screened for in newborns in all states in the United States and in many countries around the world. This is the story of one laboratory's work in bringing basic science research from the discovery of the disorder to its translation into clinical medicine and its impact on the individuals with the disorder and their families.
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forty eight novel mutations causing Biotinidase Deficiency
Molecular Genetics and Metabolism, 2016Co-Authors: Melinda Procter, Barry WolfAbstract:Biotinidase Deficiency is an autosomal recessively inherited disorder that results in the inability to recycle the vitamin biotin and is characterized by neurological and cutaneous symptoms. The symptoms can be ameliorated or prevented by administering pharmacological doses of biotin. Since 2008, approximately 300 samples have been submitted to ARUP's Molecular Sequencing Laboratory for Biotinidase mutation analysis. Of these, 48 novel alterations in the Biotinidase gene have been identified. Correlating the individual's serum enzymatic activity with the genotype, we have been able to determine the effect of the novel alteration on enzyme activity and, thereby, determine its likelihood of being pathogenic in 44 of these individuals. The novel mutations and uncertain alterations have been added to the database established by ARUP (http://arup.utah.edu/database/BTD/BTD_welcome.phps) to help clinicians make decisions about management and to better counsel their patients based on their genotypes.
Mubeccel Demirkol - One of the best experts on this subject based on the ideXlab platform.
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Biotinidase Deficiency novel mutations and their biochemical and clinical correlates
Human Mutation, 2005Co-Authors: Barry Wolf, Miriam G Blitzer, Mubeccel Demirkol, Kevin P. Jensen, Bruce Barshop, Martha D Carlson, David R Goudie, Gulden Gokcay, Tolunay Baykal, F DemirAbstract:Biotinidase Deficiency is a defect in the recycling of the vitamin biotin. Biotin supplementation can markedly improve the neurological and cutaneous symptoms of affected children and prevent symptoms in children identified by newborn screening or treated since birth. We have determined thirteen novel mutations in children with the disorder. Two nonsense mutations, eight single missense mutations, three allelic double missense mutations, and two are polymorphisms were identified in the Biotinidase gene (BTD). One of the missense mutations, c.734G>A (p. C245Y), is the first to be reported that alters the cysteine in the putative location crucial for ester formation and binding of the biotinyl-moiety in the active site of the enzyme. These mutations add to the growing list of mutations that are helping to delineate structure/function relationships of the enzyme.
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seventeen novel mutations that cause profound Biotinidase Deficiency
Molecular Genetics and Metabolism, 2002Co-Authors: Barry Wolf, Mubeccel Demirkol, G Huner, Tolga Baykal, M O Rolland, Celia Perezcerda, Magdalena Ugarte, Kevin P. Jensen, Priscille Divry, Rachel StraussbergAbstract:We report 17 novel mutations that cause profound Biotinidase Deficiency. Six of the mutations are due to deletions, whereas the remaining 11 mutations are missense mutations located throughout the gene and encode amino acids that are conserved in mammals. Our results increase the total number of different mutations that cause Biotinidase Deficiency to 79. These additional mutations will undoubtedly be helpful in identifying structure/function relationships once the three-dimensional structure of Biotinidase is determined.
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partial Biotinidase Deficiency is usually due to the d444h mutation in the Biotinidase gene
Human Genetics, 1998Co-Authors: Katie L. Swango, Mubeccel Demirkol, G Huner, Andreas Schulze, Jolanta Sykutcegielska, Ewa Pronicka, Barry WolfAbstract:Newborn screening for Biotinidase Deficiency has identified children with profound Biotinidase Deficiency ( C, which substitutes a histidine for aspartic acid444 (D444H) in one allele of the Biotinidase gene. We have previously estimated that the D444H mutation results in 48% of normal enzyme activity for that allele and occurs with an estimated frequency of 0.039 in the general population. The D444H mutation in Biotinidase Deficiency is similar to the Duarte variant in galactosemia. The D444H mutation in one allele in combination with a mutation for profound Deficiency in the other allele is the common cause of partial Biotinidase Deficiency.
Kevin P. Jensen - One of the best experts on this subject based on the ideXlab platform.
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hearing loss in Biotinidase Deficiency genotype phenotype correlation
The Journal of Pediatrics, 2007Co-Authors: Hatice Serap Sivri, Kevin P. Jensen, Turgay Coskun, Aysegul Tokatli, Gulsum Aydan Genc, Ali Dursun, Halil Ibrahim Aydin, Levent Sennaroglu, Erol Belgin, Barry WolfAbstract:Children with symptoms of profound Biotinidase Deficiency with null mutations are more likely to have hearing loss develop than those with missense mutations, even if not treated for a period of time. Hearing loss appears to be preventable in children with null mutations if treatment is initiated soon after birth.
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Biotinidase Deficiency novel mutations and their biochemical and clinical correlates
Human Mutation, 2005Co-Authors: Barry Wolf, Miriam G Blitzer, Mubeccel Demirkol, Kevin P. Jensen, Bruce Barshop, Martha D Carlson, David R Goudie, Gulden Gokcay, Tolunay Baykal, F DemirAbstract:Biotinidase Deficiency is a defect in the recycling of the vitamin biotin. Biotin supplementation can markedly improve the neurological and cutaneous symptoms of affected children and prevent symptoms in children identified by newborn screening or treated since birth. We have determined thirteen novel mutations in children with the disorder. Two nonsense mutations, eight single missense mutations, three allelic double missense mutations, and two are polymorphisms were identified in the Biotinidase gene (BTD). One of the missense mutations, c.734G>A (p. C245Y), is the first to be reported that alters the cysteine in the putative location crucial for ester formation and binding of the biotinyl-moiety in the active site of the enzyme. These mutations add to the growing list of mutations that are helping to delineate structure/function relationships of the enzyme.
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newborn screening for Biotinidase Deficiency in brazil biochemical and molecular characterizations
Brazilian Journal of Medical and Biological Research, 2004Co-Authors: Eurico Camargo Neto, Jaqueline Schulte, R Rubim, Eduardo Lewis, J Demari, Cristina D Castilhos, A Brites, Kevin P. Jensen, Roberto Giugliani, Barry WolfAbstract:Biotinidase Deficiency is an inherited metabolic disorder characterized by neurological and cutaneous symptoms. Fortunately, it can be treated and the symptoms prevented by oral administration of the vitamin biotin. Using dried blood-soaked filter paper cards, Biotinidase activity was determined in the sera of 225,136 newborns in Brazil. Mutation analysis performed on DNA from 21 babies with low serum Biotinidase activity confirmed that 3 had profound Biotinidase Deficiency (less than 10% of mean normal sera Biotinidase activity), 10 had partial Biotinidase Deficiency (10 to 30% of mean normal serum activity), 1 was homozygous for partial Biotinidase Deficiency, 4 were heterozygous for either profound or partial Deficiency, and 3 were normal. Variability in serum enzyme activities and discrepancies with mutation analyses were probably due to inappropriate handling and storage of samples sent to the laboratory. Obtaining an appropriate control serum at the same time as that of the suspected child will undoubtedly decrease the false-positive rate (0.09%). Mutation analysis can be used to confirm the genotype of these children. The estimated incidence of Biotinidase Deficiency in Brazil is about 1 in 9,000, higher than in most other countries. Screening and treatment of Biotinidase Deficiency are effective and warranted. These results strongly suggest that Biotinidase Deficiency should be included in the newborn mass screening program of Brazil.
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seventeen novel mutations that cause profound Biotinidase Deficiency
Molecular Genetics and Metabolism, 2002Co-Authors: Barry Wolf, Mubeccel Demirkol, G Huner, Tolga Baykal, M O Rolland, Celia Perezcerda, Magdalena Ugarte, Kevin P. Jensen, Priscille Divry, Rachel StraussbergAbstract:We report 17 novel mutations that cause profound Biotinidase Deficiency. Six of the mutations are due to deletions, whereas the remaining 11 mutations are missense mutations located throughout the gene and encode amino acids that are conserved in mammals. Our results increase the total number of different mutations that cause Biotinidase Deficiency to 79. These additional mutations will undoubtedly be helpful in identifying structure/function relationships once the three-dimensional structure of Biotinidase is determined.
Xuefan Gu - One of the best experts on this subject based on the ideXlab platform.
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diagnosis treatment follow up and gene mutation analysis in four chinese children with Biotinidase Deficiency
Journal of Inherited Metabolic Disease, 2009Co-Authors: Jun Ye, Y. Wang, Huan Zhang, Ting Wang, Xuefan GuAbstract:Objective: To report the clinical course and explore the gene mutation spectrum of four Chinese children with Biotinidase Deficiency. Methods: Four Chinese patients aged 4 months to 8 years were referred to this study. Tandem mass spectrometry, gas chromatography–mass spectrometry and the determination of Biotinidase activities were performed for selective screening of Biotinidase Deficiency. Four patients with Biotinidase Deficiency were diagnosed, treated with biotin and followed. Results: (1) Four patients with Biotinidase Deficiency were diagnosed by characteristic metabolites, such as elevated blood levels of 3-hydroxyisovalerylcarnitine (6.22 ± 3.1 μmol/L), elevated 3-methylcrontonylglycine, methylcitrate and 3-hydroxypropionate in urine and very low Biotinidase activities. (2) These patients have been treated with biotin for 1–8 years; two of them still have mental retardation, and two have irreversible hearing or vision disability. (3) In the four patients, six different mutations in the Biotinidase gene were identified: c.98G:del7ins3, c.1369G>A (p. V457M), c.1384delA, c.1493_1494insT, c.1284C>A (p.Y428X) and c.1157G>A (p.W386X). The latter four mutations are novel variations. Seven out of eight mutations are located on exon 4 of the Biotinidase gene. Conclusions: Early recognition of Biotinidase Deficiency is crucial to avoid permanent damage. Determination of Biotinidase activity should be included in neonatal screening in China. Exon 4 may be a hot-spot for Biotinidase gene mutations in Chinese patients. Four novel gene variations may be disease-causing mutations and should be confirmed by expression studies.
G Huner - One of the best experts on this subject based on the ideXlab platform.
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seventeen novel mutations that cause profound Biotinidase Deficiency
Molecular Genetics and Metabolism, 2002Co-Authors: Barry Wolf, Mubeccel Demirkol, G Huner, Tolga Baykal, M O Rolland, Celia Perezcerda, Magdalena Ugarte, Kevin P. Jensen, Priscille Divry, Rachel StraussbergAbstract:We report 17 novel mutations that cause profound Biotinidase Deficiency. Six of the mutations are due to deletions, whereas the remaining 11 mutations are missense mutations located throughout the gene and encode amino acids that are conserved in mammals. Our results increase the total number of different mutations that cause Biotinidase Deficiency to 79. These additional mutations will undoubtedly be helpful in identifying structure/function relationships once the three-dimensional structure of Biotinidase is determined.
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partial Biotinidase Deficiency is usually due to the d444h mutation in the Biotinidase gene
Human Genetics, 1998Co-Authors: Katie L. Swango, Mubeccel Demirkol, G Huner, Andreas Schulze, Jolanta Sykutcegielska, Ewa Pronicka, Barry WolfAbstract:Newborn screening for Biotinidase Deficiency has identified children with profound Biotinidase Deficiency ( C, which substitutes a histidine for aspartic acid444 (D444H) in one allele of the Biotinidase gene. We have previously estimated that the D444H mutation results in 48% of normal enzyme activity for that allele and occurs with an estimated frequency of 0.039 in the general population. The D444H mutation in Biotinidase Deficiency is similar to the Duarte variant in galactosemia. The D444H mutation in one allele in combination with a mutation for profound Deficiency in the other allele is the common cause of partial Biotinidase Deficiency.