Disease relevance of BTD

• BTD gene-disease database  
• The D444H mutation in biotinidase deficiency is similar to the Duarte variant in galactosemia [1].
• Examination of the signal peptide region of human biotinidase using a baculovirus expression system [2].
• A genomic clone, containing three exons that code for the mature enzyme, was obtained by screening a human genomic bacteriophage library with the biotinidase cDNA by plaque hybridization [3].
• The recent finding that biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency was stimulated new interest in the inherited disorders of biotin-dependent carboxylases [4].
• Since screening and treatment are both inexpensive and effective and the incidence of the disease is well within the range of that of other metabolic diseases for which screening is performed, biotinidase deficiency should be added to the group of metabolic diseases for which screening is done in the neonatal period [5].

Psychiatry related information on BTD

• Moderate mental retardation might represent a possible manifestation of cerebral dysfunction in patients with profound biotinidase deficiency [6].

High impact information on BTD

• Biotinidase cleaves biocytin to biotin and lysine, thereby completing the biotin cycle [7].
• We have recently isolated and characterized the cDNA for normal human biotinidase and localized the gene to chromosome 3p25 (ref. 9). We have now identified the first mutation that causes profound biotinidase deficiency [7].
• Deficient biotinidase activity in late-onset multiple carboxylase deficiency [8].
• Biotinidase deficiency associated with severe combined immunodeficiency [9].
• 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 [10].

Chemical compound and disease context of BTD

• In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels [11].
• OBJECTIVE: Since biotinidase is mainly produced in the liver and partial biotinidase deficiency causes dermatological manifestations, seborrheic dermatitis, alopecia etc., isotretinoin side effects in relation to biotinidase activity were studied [12].
• Children with juvenile-onset multiple carboxylase deficiency lack biotinidase activity (biotinamide amidohydrolase, EC 3.5.1.12) in the liver and other tissues [13].
• A definitive diagnosis could be made in 7 of 9 patients studied up to now: 4 patients suffered from biotin-nonresponsive isolated PCC-deficiency, and 3 patients from biotin-responsive multiple carboxylase deficiency caused by deficient biotinidase activity [14].
• Urinary biotinidase and alanine excretion in patients with insulin-dependent diabetes mellitus [15].

Biological context of BTD

• Localization of serum biotinidase (BTD) to human chromosome 3 in band p25 [16].
• Thus far 61 mutations in three of the four exons of the BTD and one mutation in an intron gene that cause profound BTD deficiency have been reported [17].
• The BTD gene is localized to chromosome 3p25 [17].
• Biotinidase (EC 3.5.1.12) catalyzes the hydrolysis of biocytin, the product of biotin-dependent carboxylase degradation, to biotin and lysine [18].
• Comparison of the open reading frame with the known biotinidase tryptic peptides and recognition of the expressed protein encoded by this cDNA by monoclonal antibodies prepared against purified biotinidase demonstrated the identity of this cDNA [18].

Anatomical context of BTD

• Northern analysis indicated the presence of biotinidase mRNA in human heart, brain, placenta, liver, lung, skeletal muscle, kidney, and pancreas [18].
• Aberrant biotinidase protein was not detectable in extracts of fibroblasts from a child who is homozygous for the R538C mutation, but was present in less than normal concentration in identical extracts treated with beta-mercaptoethanol [19].
• Biotinidase in human breast milk [20].
• We report the first case of biotinidase deficiency with basal ganglia calcifications [21].
• However, biotinidase activity in colostrum was about five times higher than that of mature milk [20].

Associations of BTD with chemical compounds

• Biotinidase (BTD) is the only enzyme that can cleave biocytin, a product of the proteolytic digestion of holocarboxylases [17].
• Biotinidase-deficient children cannot recycle endogenous biotin, an essential water-soluble B vitamin [7].
• This mutation results in the substitution of a cysteine for arginine538 (designated R538C) and was found in 10 of 30 symptomatic children with profound biotinidase deficiency, 5 of whom also have the G98:d7i3 mutation [19].
• We found that 18 of 19 randomly selected individuals with partial deficiency have the transversion missense mutation G1330>C, which substitutes a histidine for aspartic acid444 (D444H) in one allele of the biotinidase gene [1].
• Arg538 to Cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children [19].

Physical interactions of BTD

• With HPLC biotinidase assay instead of colorimetric method and using non-ionic surfactant, 110-kDa biotinidase was discovered and co-purified in addition to the previously identified 76-kDa biotinidase [22].

Other interactions of BTD

• Sequences of tryptic peptides of the purified human serum enzyme were used to design oligonucleotide primers for polymerase chain reaction amplification from human hepatic total RNA to generate putative biotinidase cDNA fragments [18].
• Neither the Notch1 ankyrin domain (ANK) nor C-terminal region contributes binding energy towards BTD [23].
• Another large multicenter trial also demonstrated that celecoxib 200 mg BTD and 400 mg BID is as effective as naproxen 500 mg BID in patients with rheumatoid arthritis (RA) [24].
• Lysine residues in N-terminal and C-terminal regions of human histone H2A are targets for biotinylation by biotinidase [25].
• OBJECTIVE: Multiple carboxylase deficiency (MCD, MIM:253270) is a common organic aciduria and caused by deficiency of either biotinidase or holocarboxylase synthetase (HLCS; EC 6.3.4.10) [26].

Analytical, diagnostic and therapeutic context of BTD

• To obtain a clone containing the most 5' exon of the biotinidase cDNA, a human PAC library by PCR was screened [3].
• Electrophoresis, scattering, and titration calorimetry indicate that NICD and BTD combine to form a 1:1 heterodimer [23].
• Radiation hybrids and haplotype analysis of markers within this region suggest that BTD is located within a 0.1-cM region flanked by D3S3510 and D3S1286 [27].
• These results of the BTD study suggest that future case/control studies investigating power frequency magnetic fields might wish to include measurements of 180 Hz or harmonic magnetic fields in order to examine their associations (if any) with disease status [28].
• Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program [5].

References