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Clinical Biochemistry May 2023This study set out to examine pre-analytical factors affecting the frequency of positive results in newborn screening for biotinidase deficiency. This investigation was...
This study set out to examine pre-analytical factors affecting the frequency of positive results in newborn screening for biotinidase deficiency. This investigation was prompted by an increase in the annual screen positive rate for biotinidase deficiency in Ontario from 2.65x10 in 2016 to 6.57x10 in 2017. Season and trend decomposition was used to separate seasonality from an underlying trend in the time series of biotindase activity measurements for the period 2014-01-12 to 2019-07-27 (n = 798,770). This analysis revealed a marked seasonal effect (winter = median + ⩽ 17 MRU, summer = mean - ⩽20 MRU) and a non-linear negative trend. Seasonal temperature was correlated with biotinidase results (Pearson's r = 0.79) but not with the observed negative trend (Pearson's r = 0.0025). Time series analysis of biotinidase results grouped by print lot of filter paper revealed that recently printed filter paper cards inhibit biotinidase and that this inhibition resolved over time. This study demonstrates that biotindase activity is inhibited by both increased seasonal temperature and collection on newly printed filter cards.
Topics: Humans; Infant, Newborn; Biotinidase; Biotinidase Deficiency; Seasons; Temperature; Neonatal Screening
PubMed: 35398329
DOI: 10.1016/j.clinbiochem.2022.03.010 -
Indian Pediatrics Sep 2014To assess feasibility and recall rates for newborn screening for congenital hypothyroidism, galactosemia and biotinidase deficiency in a predominantly rural and inner...
OBJECTIVE
To assess feasibility and recall rates for newborn screening for congenital hypothyroidism, galactosemia and biotinidase deficiency in a predominantly rural and inner city population in and around the City of Lucknow in Uttar Pradesh, India.
DESIGN
Prospective observational study.
SETTING
Two tertiary-care and 5 district hospitals in and around Lucknow.
PARTICIPANTS
All babies born in above hospitals during the study period.
METHODS
Heel prick samples were collected after 24 hours of life. Dried blood spot TSH, total galactose and biotinidase were assayed by immunofluorometry. Age related cut-offs were applied for recall for TSH. For galactosemia and biotinidase deficiency, manufacturer-suggested recall cut-offs used initially were modified after analysis of initial data.
MAIN OUTCOME MEASURE
Recall rate for hypothyroidism, galactosemia and biotinidase deficiency.
RESULTS
Screening was carried out for 13426 newborns, 73% of all deliveries. Eighty-five percent of those recalled for confirmatory sampling responded. Using fixed TSH cut off of 20 mIU/L yielded high recall rate of 1.39%, which decreased to 0.84% with use of age-related cut-offs. Mean TSH was higher in males, and in low birth weight and vaginally delivered babies. Eleven babies had congenital hypothyroidism. Recall rates with modified cut-offs for galactosemia and biotinidase deficiency were 0.32% and 0.16%, respectively.
CONCLUSIONS
An outreach program for newborn screening can be successfully carried out in similar socio-cultural settings in India. For hypothyroidism, the high recall rate due to early discharge was addressed by age-related cut-offs.
Topics: Biotinidase Deficiency; Congenital Hypothyroidism; Dried Blood Spot Testing; Female; Galactosemias; Humans; India; Infant, Newborn; Male; Neonatal Screening; Prospective Studies; Reference Values; Thyrotropin
PubMed: 25228601
DOI: 10.1007/s13312-014-0485-x -
Genetics in Medicine : Official Journal... Mar 2015Biotinidase deficiency, if untreated, usually results in neurological and cutaneous symptoms. Biotin supplementation markedly improves and likely prevents symptoms in...
PURPOSE
Biotinidase deficiency, if untreated, usually results in neurological and cutaneous symptoms. Biotin supplementation markedly improves and likely prevents symptoms in those treated early. All states in the United States and many countries perform newborn screening for biotinidase deficiency. However, there are few studies about the outcomes of the individuals identified by newborn screening.
METHODS
We report the outcomes of 142 children with biotinidase deficiency identified by newborn screening in Michigan over a 25-year period and followed in our clinic; 22 had profound deficiency and 120 had partial deficiency.
RESULTS
Individuals with profound biotinidase and partial deficiency identified by newborn screening were started on biotin therapy soon after birth. With good compliance, these children appeared to have normal physical and cognitive development. Although some children exhibited mild clinical problems, these are unlikely attributable to the disorder. Biotin therapy appears to prevent the development of neurological and cutaneous problems in our population.
CONCLUSION
Individuals with biotinidase deficiency ascertained by newborn screening and treated since birth appeared to exhibit normal physical and cognitive development. If an individual does develop symptoms, after compliance and dosage issues are excluded, then other causes must be considered.Genet Med 17 3, 205-209.
Topics: Biotin; Biotinidase; Biotinidase Deficiency; DNA Mutational Analysis; Humans; Infant, Newborn; Michigan; Neonatal Screening; Retrospective Studies; Treatment Outcome; Vitamin B Complex
PubMed: 25144890
DOI: 10.1038/gim.2014.104 -
Annals of Medicine and Surgery (2012) May 2023Biotinidase deficiency (BTD) is an autosomal recessive disorder and causes the deficiency of four biotin-containing carboxylases. The prevalence is estimated at 1 in...
UNLABELLED
Biotinidase deficiency (BTD) is an autosomal recessive disorder and causes the deficiency of four biotin-containing carboxylases. The prevalence is estimated at 1 in 60 000 births. BTD is associated with a wide spectrum of clinical manifestations, including abnormalities of the neurological, dermatological, immunological, and ophthalmological systems. Spinal cord demyelination as a manifestation of BTD has been infrequently described.
CASE PRESENTATION
The authors present a case of 2.5-year-old boy complained of progressive weakness in all four limbs, with difficulties in breathing.
CLINICAL DISCUSSION
Abdominal examination revealed hepatomegaly and splenomegaly. Also, her parents were first-degree cousins. Therefore, tandem mass spectroscopy and urine organic acid analysis were planned to exclude metabolic disorders. Urinary organic acid analysis revealed elevated levels of methylmalonic acid and 3-hydroxyisovaleric acid. Serum biotinidase activity was found to be 3.9 nmol/min/ml. Oral biotin at a dose of 1 mg/kg daily was initiated. A marked improvement of his neurological deficit was noted over a period of 15 days after treatment and cutaneous manifestations resolved within 3 weeks.
CONCLUSION
Myelopathy due to BTD is a challenging diagnosis. Spinal cord impairment is a rare complication of this disease and is frequently unrecognized. BTD should be included in the differential diagnosis of children presenting with demyelinating spinal cord disease.
PubMed: 37229044
DOI: 10.1097/MS9.0000000000000099 -
Genetics in Medicine : Official Journal... Jul 2010Biotinidase deficiency is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences if untreated....
Biotinidase deficiency is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences if untreated. Fortunately, the clinical features of the disorder can be ameliorated or prevented by administering pharmacological doses of the vitamin biotin. Newborn screening and confirmatory diagnosis of biotinidase deficiency encompasses both enzymatic and molecular testing approaches. These guidelines were developed to define and standardize laboratory procedures for enzymatic biotinidase testing, to delineate situations for which follow-up molecular testing is warranted, and to characterize variables that can influence test performance and interpretation of results.
Topics: Biotinidase; Biotinidase Deficiency; Humans; Infant, Newborn; Mutation; Neonatal Screening
PubMed: 20539236
DOI: 10.1097/GIM.0b013e3181e4cc0f -
Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations.Brazilian Journal of Medical and... Mar 2004Biotinidase deficiency is an inherited metabolic disorder characterized by neurological and cutaneous symptoms. Fortunately, it can be treated and the symptoms prevented...
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.
Topics: Biotinidase Deficiency; Brazil; Female; Genotype; Humans; Incidence; Infant, Newborn; Male; Mutation; Neonatal Screening
PubMed: 15060693
DOI: 10.1590/s0100-879x2004000300001 -
Cureus May 2020Biotinidase deficiency (BTD) is a rare yet treatable metabolic autosomal recessive (AR) disorder in which the body is unable to recycle the vitamin biotin. Early...
Biotinidase deficiency (BTD) is a rare yet treatable metabolic autosomal recessive (AR) disorder in which the body is unable to recycle the vitamin biotin. Early diagnosis and treatment can be life-saving, but some symptoms of the disease are irreversible, and the condition can even prove to be fatal if not correctly diagnosed and managed. Here we present a case of a six-month-old child who presented with cough, fever, and difficulty in breathing. Respiratory examination revealed deep subcostal and intercostal recessions, bilateral crepitations, and wheezes. On central nervous system (CNS) examination, the baby had a low Glasgow Coma Scale (GCS) score of 10 while the tone was decreased, and bulk was increased in all four limbs. Chest X-ray revealed haziness at the right middle and lower lobes. Antibiotics were started keeping pneumonia, bronchiolitis, and sepsis in mind along with an initial diagnosis of inborn error of metabolism (IEM). As the patient's condition deteriorated, nasal bubble continuous positive airway pressure (CPAP) and nebulization were provided and later put on a ventilator. Arterial blood gases (ABGs) showed severe metabolic acidosis and compensatory respiratory alkalosis with an anion gap of 15. Urine profile for organic acid was performed, and the diagnosis of sepsis with BTD was made. Unfortunately, our patient expired on the fourth day of admission before a biotin injection could be searched and administered. Moreover, our patient was also suspected of a possible Sotos syndrome, which is a rare genetic disorder characterized by excessive growth in the initial years of life. The case highlights the significance of the diagnosis of such metabolic disorders in the natal period of life and their immediate management.
PubMed: 32523854
DOI: 10.7759/cureus.8000 -
Molecular Genetics and Metabolism Jun 2018All States screen for biotinidase deficiency and galactosemia, and X-linked adrenoleukodystrophy (X-ALD) has recently been added to the Recommended Uniform Screening...
Multiplex tandem mass spectrometry assay for newborn screening of X-linked adrenoleukodystrophy, biotinidase deficiency, and galactosemia with flexibility to assay other enzyme assays and biomarkers.
All States screen for biotinidase deficiency and galactosemia, and X-linked adrenoleukodystrophy (X-ALD) has recently been added to the Recommended Uniform Screening Panel (RUSP).We sought to consolidate these tests by combining them into a single multiplex tandem mass spectrometry assay as well as to improve the current protocol for newborn screening of galactosemia.A 3 mm punch of a dried blood spot (DBS) was extracted with organic solvent for analysis of the C26:0-lysophosphatidylcholine biomarker for X-ALD.An additional punch was used to assay galactose-1-phosphate uridyltransferase (GALT) and biotinidase.All assays were combined for a single injection for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (2.3 min per sample).The GALT LC-MS/MS assay does not give a false positive for galactosemia if glucose-6-phosphate dehydrogenase is deficient.The multiplex assay shows acceptable reproducibility and provides for rapid analysis of X-ALD, biotinidase deficiency, and galactosemia.The throughput and ease of sample preparation are acceptable for newborn screening laboratories.We also show that the LC-MS/MS assay is expandable to include several other diseases including Pompe and Hurler diseases (enzymatic activities and biomarkers).Because of consolidation of assays, less manpower is needed compared to running individual assays on separate platforms.The flexibility of the LC-MS/MS platform allows each newborn screening laboratory to analyze the set of diseases offered in their panel.
Topics: Adrenoleukodystrophy; Adult; Biomarkers; Biotinidase; Biotinidase Deficiency; Dried Blood Spot Testing; Enzyme Assays; Galactosemias; Humans; Infant, Newborn; Neonatal Screening; Tandem Mass Spectrometry; UTP-Hexose-1-Phosphate Uridylyltransferase
PubMed: 29680633
DOI: 10.1016/j.ymgme.2018.03.012 -
Journal of Pediatric Genetics Sep 2022Biotinidase deficiency (BD) is a rare treatable cause of neurometabolic disorders. It is an autosomal recessive disorder that manifests with cutaneous and neurological...
Biotinidase deficiency (BD) is a rare treatable cause of neurometabolic disorders. It is an autosomal recessive disorder that manifests with cutaneous and neurological manifestations. Spinal cord involvement is uncommon with only a few cases reported in the literature. A 6-year-old female child presented with progressive difficulty in walking since 2 months. At 6 months of age, the child was elsewhere evaluated for global developmental delay and suspected as metabolic disorders and started on megavitamins, following which the child was improved. For the past 2 years, she has stopped medicines. On examination, irritable, alopecia, eczema, hypotonia, and power of two-fifths in all four limbs, and exaggerated deep tendon reflexes. The magnetic resonance imaging (MRI) brain and spine showed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in periaqueductal gray matter, dorsal midbrain, pons, medulla, and cervical cord. She was suspected to have BD and confirmed by low enzyme levels and pathogenic variant in . She was started on biotin supplements that resulted clinically dramatic improvement and MRI became normal within 4 weeks. Any child presenting with acute flaccid paralysis with brainstem and spinal cord noncompressive lesions on MRI, rare treatable conditions like BD should be considered in developing countries, like India, where still no universal newborn screening facilities are available.
PubMed: 35990026
DOI: 10.1055/s-0040-1718537 -
Genetics in Medicine : Official Journal... Oct 2017Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical...
Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory scientists and geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Biotinidase deficiency is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences if untreated. Fortunately, the clinical features of the disorder can be ameliorated or prevented by administering pharmacological doses of the vitamin biotin. Newborn screening and confirmatory diagnosis of biotinidase deficiency encompasses both enzymatic and molecular testing approaches. These guidelines were developed to define and standardize laboratory procedures for enzymatic biotinidase testing, to delineate situations for which follow-up molecular testing is warranted, and to characterize variables that can influence test performance and interpretation of results.
Topics: Biotinidase; Biotinidase Deficiency; Clinical Laboratory Techniques; Female; Genetic Testing; Genetics, Medical; Genomics; Humans; Infant, Newborn; Male; Neonatal Screening; United States
PubMed: 28682309
DOI: 10.1038/gim.2017.84