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European Journal of Human Genetics :... Oct 2016Biotinidase deficiency is a rare inherited metabolic disorder that can cause severe neurological symptoms. To prevent severe clinical presentations, it was included in...
Biotinidase deficiency is a rare inherited metabolic disorder that can cause severe neurological symptoms. To prevent severe clinical presentations, it was included in the Dutch neonatal screening programme in 2007. Since then the number of cases detected has been high. This study set out to describe the incidence of the disease, the clinical and demographic characteristics of the neonates identified and the type of mutations found. In the south-western Netherlands, 304 982 neonates were screened between 2007 and 2012; and 92 were identified for further testing. Confirmatory testing revealed 6 (7%) with a profound biotinidase deficiency (<10% enzyme activity), 44 (48%) with a partial deficiency (10-30%) and 42 (46%) with normal activity (>30%). All six patients whose profound deficiency was confirmed had enzyme activities below 15% on neonatal screening. Mutation analysis was performed in 61 neonates: 5 'profound', 35 'partial' and 21 'normal'. All five 'profound' cases had two severe mutations. Comparison with the northern Netherlands showed that the frequency and types of mutation were representative for the Netherlands as a whole. The most common mutation detected was c.[1330G>C] (p.(Asp444His); 34%), which is considered to be mild, followed by three severe mutations c.[1368A>C], c.[1595C>T] and c.[1330G>C;511G>A]. Seven new mutations were identified. We conclude that neonatal screening for profound biotinidase produces a high number of false positives. Biotinidase deficiency was profound in less than 10% of cases identified. As biotinidase activity lay below 15% on neonatal screening in all such cases, the screening threshold might be reduced to 15%.
Topics: Biotinidase Deficiency; False Positive Reactions; Female; Genetic Testing; Humans; Infant, Newborn; Male; Netherlands; Sensitivity and Specificity
PubMed: 27329734
DOI: 10.1038/ejhg.2016.65 -
Journal of Personalized Medicine Jan 2020Biotinidase deficiency is an autosomal recessive metabolic disorder whose diagnosis currently depends on clinical symptoms and a biotinidase enzyme assay. This study...
Biotinidase deficiency is an autosomal recessive metabolic disorder whose diagnosis currently depends on clinical symptoms and a biotinidase enzyme assay. This study aimed to investigate the mutational status and enzymatic activity of biotinidase deficiency in seven unrelated Jordanian families including 10 patients and 17 healthy family members. Amplified DNA was analyzed by the automated Sanger sequencing method, and the enzymatic assay was performed using a colorimetric assessment. Biotinidase level was significantly lower ( < 0.001) in children compare to their non-affected family members. Genetic sequencing revealed six different mutations in Jordanian patients. One mutation was novel and located in exon 4, which could be a prevalent mutation for biotinidase deficiency in the Jordanian population. Identification of these common mutations and combing the enzymatic activity with genotypic data will help clinicians with regard to better genetic counseling and management through implementing prevention programs in the future.
PubMed: 31973013
DOI: 10.3390/jpm10010004 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Feb 2022Multiple carboxylase deficiency (MCD) includes autosomal recessive holocarboxylase synthetase (HLCS) deficiency and biotinidase (BTD) deficiency, which are caused by and...
Multiple carboxylase deficiency (MCD) includes autosomal recessive holocarboxylase synthetase (HLCS) deficiency and biotinidase (BTD) deficiency, which are caused by and gene mutations respectively. Neonatal screening for HLCS deficiency is based on 3-hydroxyisovaleryl carnitine in dry blood filter paper, and BTD deficiency is based on BTD activity determination. HLCS deficiency and BTD deficiency are characterized by neurocutaneous syndrome and organic aciduria, however, they are different in onset age, neurological symptoms and metabolic decompensation, which needed to be differentiated from acquired biotin deficiency or other genetic metabolic diseases. The diagnosis of the disease requires a combination of biochemical characteristics of hematuria, enzyme activity determination and genetic test. Routine biotin doses are effective for most MCD patients. This consensus is intended to benefit early screening and diagnosis of MCD.
Topics: Biotin; Biotinidase Deficiency; Carbon-Nitrogen Ligases; Consensus; Holocarboxylase Synthetase Deficiency; Humans; Infant, Newborn; Multiple Carboxylase Deficiency; Neonatal Screening
PubMed: 35576117
DOI: 10.3724/zdxbyxb-2022-0164 -
Genetics in Medicine : Official Journal... Jun 2012Biotinidase recycles the vitamin biotin. Biotinidase deficiency is an autosomal recessively inherited neurocutaneous disorder. The symptoms of the disorder can be... (Review)
Review
Biotinidase recycles the vitamin biotin. Biotinidase deficiency is an autosomal recessively inherited neurocutaneous disorder. The symptoms of the disorder can be successfully treated or prevented by administering pharmacological doses of biotin. The biotinidase gene (BTD) has been cloned and sequenced; its genomic organization has been determined and more than 150 mutations have been identified. The disorder meets the major criteria for newborn screening and is being universally adopted in the United States and in many countries around the world. Newborn screening will limit our understanding about the natural history of the disorder. Regardless, the disorder is an ideal example of an inherited metabolic disorder that if untreated can result in major disabilities, but if identified early can be readily treated by the oral administration of a vitamin.
Topics: Adult; Biotin; Biotinidase; Biotinidase Deficiency; Child; Child, Preschool; Diet Therapy; Humans; Infant, Newborn; Mutation; Neonatal Screening
PubMed: 22241090
DOI: 10.1038/gim.2011.6 -
Molecular Genetics and Metabolism... Mar 2020Biotinidase deficiency (BD) is an autosomal recessively inherited disorder characterized by developmental delay, seizures, hypotonia, ataxia, skin rash/eczema, alopecia,...
INTRODUCTION
Biotinidase deficiency (BD) is an autosomal recessively inherited disorder characterized by developmental delay, seizures, hypotonia, ataxia, skin rash/eczema, alopecia, conjunctivitis/visual problem/optic atrophy and metabolic acidosis. Delayed diagnosis may lead to irreversible neurological damage.
METHODOLOGY
Clinically suspected patients were screened for biotinidase level by a fluorometry method. Profound BD patients were confirmed by mutation analysis of gene.
RESULTS
9 patients had biotinidase activity of less than 77 U. 3 patients (33%) had profound BD while 6 patients (67%) had partial BD. Compound heterozygous mutations were detected at c.98_104delinsTCC p.(Cys33Phefs*36) in Exon 2 and c.833T>C p.(Leu278Pro) in Exon 4 in two patients and a homozygous mutation at c.98_104delinsTCC p.(Cys33Phefs*36) in Exon 2 in another patient.
CONCLUSION
Correct diagnosis lead to early treatment and accurate management of patient. Biochemical screening of BD in symptomatic child is prerequisite to determine enzyme status however molecular confirmation is vital in differentiating individuals with profound biotinidase deficiency from partial biotinidase deficiency and also individuals' carriers.
PubMed: 32300527
DOI: 10.1016/j.ymgmr.2019.100548 -
Frontiers in Pediatrics 2021Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and...
Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients. We analyzed data of patients identified by the Regional Centre for Newborn Screening of Verona and followed by the Inherited Metabolic Disease Unit of Verona and Neonatal Intensive Care Unit of Bolzano, Italy, from 2014 to 2020. Thirty-seven patients were diagnosed by NBS (five profound and 32 partial BD), with a total incidence of 1:5,996. All were started on biotin at diagnosis and presented no symptoms at follow-up. Analysis of parents and siblings led to identification of five asymptomatic patients with partial BD: one asymptomatic parent and four young siblings. Genetic analysis of the gene identified 17 different genotypes and one mutation not previously known. Our data confirm that NBS introduction had a dramatic impact on BD diagnosis, and the incidence has increased significantly compared to other areas. Partial defects are more common than profound and have a distinctive genotype. Partial BD treatment is still controversial even at what dose of biotin and for how long. At the end, BD treatment is very easy and inexpensive and prevents severe neurological damage. Sharing experiences is essential to achieving guidelines for treatment and follow-up and a better genotype-phenotype correlation.
PubMed: 34136440
DOI: 10.3389/fped.2021.661416 -
JPMA. the Journal of the Pakistan... Mar 2022Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well... (Review)
Review
Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative review was planned to provide a perspective with evidence in favour of starting newborn screening for different disorders. The programme project should be initiated nationwide, taking one disorder, congenital hypothyroidism, as the prototype and a newborn screening panel can then be extended to include other disorders. A task force should be set up to recommend disorders to be included in the panel, develop the national plan policies, and define procedures to strengthen the testing.
Topics: Congenital Hypothyroidism; Humans; Infant, Newborn; Neonatal Screening; Pakistan
PubMed: 35320237
DOI: 10.47391/JPMA.01181 -
JPMA. the Journal of the Pakistan... Jan 2022To determine the reference interval of biotinidase activity in healthy neonates.
OBJECTIVE
To determine the reference interval of biotinidase activity in healthy neonates.
METHODS
The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from May to November 2019, and comprised blood samples collected from healthy neonates aged 2-6 days. The samples were collected on filter paper and analysed on genetic screening processor based on dissociation-enhanced lanthanide flouroimmunoassay. Data was analysed using SPSS 21.
RESULTS
Of the 120 dried blood spot specimens, 81(67.5%) were from male babies and 39(32.5%) from female babies. Reference interval for biotinidase activity, based on 2.5th and 97.5th percentiles, was from 3.0 to 11.0 nmol/ml/min.
CONCLUSIONS
Screening of newborns for biotinidase deficiency is crucial to prevent irreversible neurological damage.
Topics: Amidohydrolases; Biotinidase; Biotinidase Deficiency; Cross-Sectional Studies; Female; Humans; Infant, Newborn; Male; Neonatal Screening; Pakistan
PubMed: 35099446
DOI: 10.47391/JPMA.2167 -
Molecular Genetics and Metabolism... Dec 2020The biotinidase (BTD) enzyme is essential for recycling biotin, a water-soluble B-complex vitamin that is the coenzyme of four carboxylases involved in fatty acid...
The biotinidase (BTD) enzyme is essential for recycling biotin, a water-soluble B-complex vitamin that is the coenzyme of four carboxylases involved in fatty acid synthesis, amino acid catabolism and gluconeogenesis. If untreated, total or partial BTD deficiencies lead to an autosomal recessive inherited organic aciduria whose clinical features, mainly presenting in the first years of life, include, seizures, skin rash, and alopecia. Based on residual BTD enzyme activity it is possible to identify partial or total biotinidase deficiency. The incidence of profound and partial biotinidase deficiency worldwide is estimated to be about 1 in 60.000. We report twelve years of experience in the newborn screening of biotinidase deficiency on 466.182 neonates. When a positive screening result occurred, a clinical evaluation was made of the patient and genetic counselling was offered to the family. Molecular analysis the BTD gene was carried out in all recalled neonates. Newborn screening lead to the identification of 75 BTD deficiencies with an incidence of about 1:6.300 births, ten times higher than the reported worldwide incidence. BTD deficiency was confirmed at a genomic level in all patients, demonstrating a high frequency of the p.(Asp444His) amino acid substitution and the complex allele p.(Ala171Thr)/p.(Asp444His) in the analyzed Italian newborns. Four new mutations (two small deletions, one stop mutation and one missense mutation) and a new combined allelic alteration were identified. Our data suggests that there is a high incidence of the biotinidase defect in the Italian population, most likely due to the high frequency of certain mutations.
PubMed: 33312878
DOI: 10.1016/j.ymgmr.2020.100689 -
European Journal of Human Genetics :... Jul 2016
Review
Topics: Biotinidase; Biotinidase Deficiency; Humans
PubMed: 26577040
DOI: 10.1038/ejhg.2015.246