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Pediatric Health, Medicine and... 2020Biotinidase deficiency is an autosomal recessive inherited neurocutaneous disorder. Clinically untreated patients with BD can present with variable neurological and... (Review)
Review
Biotinidase deficiency is an autosomal recessive inherited neurocutaneous disorder. Clinically untreated patients with BD can present with variable neurological and dermatological signs, such as seizures, hypotonia, feeding problems, developmental delay, hearing loss, optic atrophy ataxia, alopecia, and skin rash. Clinical findings of patients with partial BD reported in the literature show that it can occur from infancy to adulthood. Outcomes of newborn screening programs support the fact that biotin treatment started after birth prevents patients with biotinidase deficiency from developing symptoms. Presence of late-onset cases with different clinical findings indicates that there is still much to learn about BD.
PubMed: 32440248
DOI: 10.2147/PHMT.S198656 -
Gene Sep 2016Biotinidase is the enzyme that is necessary for the recycling of the vitamin, biotin. Biotinidase deficiency is an autosomal recessively inherited metabolic disorder. If... (Review)
Review
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.
Topics: Animals; Biotin; Biotinidase; Biotinidase Deficiency; Disease Models, Animal; Gene Expression; History, 20th Century; History, 21st Century; Humans; Infant, Newborn; Mice; Mutation; Neonatal Screening; Translational Research, Biomedical; United States
PubMed: 26456103
DOI: 10.1016/j.gene.2015.10.010 -
Journal of Pediatric Genetics Mar 2023Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When... (Review)
Review
Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the gene are reported worldwide. Mutations in the gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.
PubMed: 36684547
DOI: 10.1055/s-0042-1757887 -
Molecular Genetics and Metabolism Apr 2023Biotinidase deficiency (BD) is an autosomal recessively inherited disorder that was first described in 1982. Forty years after its first description, we compiled...
BACKGROUND
Biotinidase deficiency (BD) is an autosomal recessively inherited disorder that was first described in 1982. Forty years after its first description, we compiled available clinical data on BD with the aim of generating a more comprehensive picture of this condition.
METHODS
A systematic search strategy was performed in relevant databases without limits for publication date or languages. We screened 3966 records and included 144 articles reporting individuals with BD and their clinical presentation as well as the outcomes, when available.
RESULTS
This study included 1113 individuals with BD. More than half (51.5%) of these individuals were diagnosed by newborn screening, 43.3% in presence of clinical symptoms and 5.2% due to family screening. We grouped symptomatic individuals into four main clinical presentations: neonatal-onset (<1 month; 7.9%), early childhood-onset (<2 years; 59.2%), juvenile-onset (2-16 years; 25.1%) and adult-onset (>16 years; 7.7%). BD affected five main organ systems: nervous system (67.2%), skin (53.7%), eye (34.4%), auditory (26.9%) and respiratory system (17.8%). Involvement was mainly multisystemic (82.2%) of individuals, whereas isolated system presentation was seen in only 17.2% of individuals. When reported, metabolic acidosis was present in 42.4% of symptomatic individuals and characteristic abnormal organic acid metabolites were found in 57.1%. Biotin treatment led to clinical stability or improvement in 89.2% of individuals. 1.6% of reported individuals with BD died due to non-availability of treatment or late diagnosis.
CONCLUSION
Newborn screening has had a major positive impact on the outcome of many individuals with BD. However, undiagnosed and non-treated BD remains a health concern. Given the risk of mortality or complications associated with late or missed diagnosis if newborn screening is not available, a trial of biotin should be considered in undiagnosed infants and adults exhibiting suspected clinical signs. Enzymatic activity and/or analysis of genetic variants can readily confirm the diagnosis of BD.
Topics: Infant; Infant, Newborn; Adult; Child, Preschool; Humans; Biotinidase Deficiency; Biotin; Biotinidase; Neonatal Screening; Databases, Factual
PubMed: 37027963
DOI: 10.1016/j.ymgme.2023.107560 -
Molecular Genetics and Metabolism Nov 2015Multiple symptomatic children with biotinidase deficiency have exhibited spastic para- or tetraplegia due to myelopathy with and without vision loss. Although this has... (Review)
Review
Multiple symptomatic children with biotinidase deficiency have exhibited spastic para- or tetraplegia due to myelopathy with and without vision loss. Although this has been a feature of what has been designated as delayed onset-biotinidase deficiency, myelopathy is likely also on the continuum of clinical features seen in younger children who have had these features attributed to dysfunction of the upper brain rather than of the spinal cord. Because many countries are still not screening their newborns for biotinidase deficiency, the disorder should be included in the differential diagnosis of individuals with myelopathic symptoms. Many of these children have gone weeks to months before they were correctly diagnosed with biotinidase deficiency. Rapid recognition that a child with myelopathy with and without vision loss has biotinidase deficiency will undoubtedly facilitate prompt treatment, increase the possibility of complete recovery and avoid potential residual permanent neurological damage. Newborn screening for biotinidase deficiency would avoid the delay in the diagnosis and treatment of individuals who otherwise may present with myelopathic or other neurological symptoms.
Topics: Biotinidase Deficiency; Blindness; Child; Diagnosis, Differential; Humans; Infant, Newborn; Neonatal Screening; Scotoma; Spinal Cord; Spinal Cord Diseases
PubMed: 26358973
DOI: 10.1016/j.ymgme.2015.08.012 -
Indian Journal of Otolaryngology and... Aug 2022Metabolic syndromes associated with hearing loss are rare and are characterized by specific enzyme pathway deficiencies involving lysosomal storage, peroxisomes, fatty...
Metabolic syndromes associated with hearing loss are rare and are characterized by specific enzyme pathway deficiencies involving lysosomal storage, peroxisomes, fatty acid enzymes, organic acids and amino acids. The deficiency of biotinidase, an enzyme involved in the metabolism of biotin, is one such rare cause of congenital hearing loss estimated at 1:60,000 newborns. The parents of a 5-year-old girl presented to the clinic with complaints that she was hard of hearing with no speech development. At age 2 she had been diagnosed with organic aciduria and hydronephrourethrosis and was operated for renal calculi. Clinical examination showed periorificial scaly skin lesions and eczematous otitis externa. An audiological evaluation showed bilateral profound SNHL. Imaging and routine investigations were unremarkable, except for a mild low anion gap metabolic acidosis. General anaesthesia involved avoidance of neuromuscular agents due to the risk of inducing hypotonia. Surgery consisted of cortical mastoidectomy followed by the facial recess approach. A standard electrode array was inserted via the round window technique and complete atraumatic insertion was achieved. Intraoperative electrode impedance and NRT tracings were good. Hearing loss in biotinidase deficiency may be expected to be of progressive nature and regular evaluation of hearing and speech is required. Cochlear implantation is currently the best available solution for severe to profound hearing loss in this disorder although the enzymatic pathology affects the entire auditory pathway. Biotin supplementation is required lifelong for its management.
PubMed: 36032817
DOI: 10.1007/s12070-020-02105-3 -
Journal of Neonatal-perinatal Medicine 2020Biotinidase deficiency is an inherited disorder of biotin metabolism that is untreated may present within the first few month of life.
INTRODUCTION
Biotinidase deficiency is an inherited disorder of biotin metabolism that is untreated may present within the first few month of life.
OBJECTIVE
We report the exceptional observation of a biotinidase deficiency in Morocco. The rarity of this pathology, its age of onset, its mode of revelation and the lack of treatment in Morocco make the particularity of this observation.
OBSERVATION
A newborn child born from a 24-year-old mother, followed by an estimated pregnancy of 37 weeks of amenorrhea according to the Farr score (morphological maturation score used for the dating of the pregnancy term). The infant presented at 7 days of life with a cutaneous-mucous eruption with icithiosic dry erythroderma of interest to the trunk, the face, the scalp associated with alopecia and depilation of the eyebrow. The biotinoidase deficiency was confirmed by its low serum concentration at 49 nka / l. The newborn died at 20 days of life before starting the specific treatment.
CONCLUSION
Biotinidase deficiency is a rare condition requiring early screening and rapid management. The delay in diagnosis and the unavailability of treatment in Morocco can have fatal consequences.
Topics: Age of Onset; Alopecia; Biotin; Biotinidase Deficiency; Consanguinity; Dermatitis, Exfoliative; Eyebrows; Fatal Outcome; Health Services Accessibility; Humans; Ichthyosis; Infant, Newborn; Intensive Care Units, Neonatal; Male; Morocco; Muscle Hypotonia; Myoclonus; Rare Diseases; Vitamin B Complex
PubMed: 31594257
DOI: 10.3233/NPM-180130 -
Molecular Genetics and Metabolism 2011Biotinidase deficiency is an autosomal recessively inherited metabolic disorder in which the enzyme, biotinidase, is defective and the vitamin, biotin, is not recycled.... (Review)
Review
Biotinidase deficiency is an autosomal recessively inherited metabolic disorder in which the enzyme, biotinidase, is defective and the vitamin, biotin, is not recycled. Individuals with biotinidase deficiency, if not treated with biotin, usually exhibit neurological and cutaneous abnormalities. Biotin treatment can ameliorate or prevent symptoms. Biotinidase deficiency meets the major criteria for inclusion in newborn screening programs. With the advent of universal newborn screening for the disorder, the "window-of-opportunity" to characterize the consequences of the untreated disease is essentially gone. To understand the neurology of biotinidase deficiency, we must depend on what is already known about symptomatic individuals with the disorder. Therefore, in this review, the neurological findings of symptomatic individuals with profound biotinidase deficiency have been compiled to catalog the characteristic features of the disorder and the consequences of biotin treatment on these findings. In addition, based on the available evidence, I have speculated on the cause of neurological problems associated with the disorder. Future studies in biotinidase-deficient animals should allow us to demonstrate more definitively if these speculations are correct.
Topics: Animals; Biotin; Biotinidase; Biotinidase Deficiency; Humans; Nervous System Diseases
PubMed: 21696988
DOI: 10.1016/j.ymgme.2011.06.001