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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 -
Journal of Inherited Metabolic Disease Jul 2019Biotin is a water-soluble vitamin that belongs to the vitamin B complex and which is an essential nutrient of all living organisms from bacteria to man. In eukaryotic... (Review)
Review
Biotin is a water-soluble vitamin that belongs to the vitamin B complex and which is an essential nutrient of all living organisms from bacteria to man. In eukaryotic cells biotin functions as a prosthetic group of enzymes, collectively known as biotin-dependent carboxylases that catalyze key reactions in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Enzyme-bound biotin acts as a vector to transfer a carboxyl group between donor and acceptor molecules during carboxylation reactions. In recent years, evidence has mounted that biotin also regulates gene expression through a mechanism beyond its role as a prosthetic group of carboxylases. These activities may offer a mechanistic background to a developing literature on the action of biotin in neurological disorders. This review summarizes the role of biotin in activating carboxylases and proposed mechanisms associated with a role in gene expression and in ameliorating neurological disease.
Topics: Amino Acids; Biotin; Biotinidase; Biotinidase Deficiency; Carbon-Carbon Ligases; Gene Expression Regulation; Humans; Infant, Newborn; Metabolism, Inborn Errors; Multiple Carboxylase Deficiency
PubMed: 30746739
DOI: 10.1002/jimd.12073 -
Giornale Italiano Di Dermatologia E... Oct 2019One of the most common micronutrient deficiencies with cutaneous findings is the vitamin B, also known as biotin, deficiency. Biotin deficiency may be due to congenital... (Review)
Review
One of the most common micronutrient deficiencies with cutaneous findings is the vitamin B, also known as biotin, deficiency. Biotin deficiency may be due to congenital lack of biotinidase, or acquired following some conditions that interfere with its absorption, such as inflammatory bowel disorders, a diet too rich in avidin, magnesium deficiency, smoking habit and treatment with broad-spectrum antibiotics, anticonvulsants and sulfonamides. This review highlights the role of biotin in the most common skin disorders such associated with biotin deficiency and an approach to their treatment. Biotin administration may improve the treatment of hair loss when deficiency is detected on the basis of a careful patient history, clinical examination and the determination of serum biotin levels. The use of biotin is rationale in seborrheic dermatitis as the vitamin intercepts the main metabolic pathways underlying the pathogenesis of the disease. Treatment with biotin could also be useful in comedonal acne characterized by a high rate of seborrhea, and may be helpful for acne treated with topical retinoids, contributing to the control of flaking and irritation. The tolerability of biotin is excellent and there is no risk of hypervitaminosis even in the case of high doses. It is important that administration is controlled by physicians and follows a medical diagnosis and prescription. Correct doses used in dermatological conditions are safe and are not at risk of interference with laboratory tests.
Topics: Alopecia; Biotin; Biotinidase; Biotinidase Deficiency; Dermatitis, Seborrheic; Humans; Skin Diseases
PubMed: 31638351
DOI: 10.23736/S0392-0488.19.06434-4 -
Journal of Pediatric Endocrinology &... Nov 2021Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase...
OBJECTIVES
Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase deficiency, and it is inherited as autosomal recessive. The aim of this study was to evaluate the cases followed up with the diagnosis of biotinidase deficiency in our unit, in terms of clinical, biochemical and genetic analyses.
METHODS
A total of 112 cases followed up in our centre with the diagnosis of biotinidase deficiency between August 2018-September 2020 were included in the study. Data were collected retrospectively.
RESULTS
A total of 112 cases (55.4% male, mean age: 2.2 ± 2.8 years) diagnosed with biotinidase deficiency were evaluated. Diagnoses were made by newborn screening in 90.2% of the cases, by family screening in 4.5%, and by investigating symptoms in 5.4%. The most frequently (27.5%) detected mutations were c.1330G>C (p.D444H)/c.1330G>C (p.D444H) homozygous mutation, followed by (13.0%) c.1330G>C (p.D444H)/c.470G>A (p.R157H) compound heterozygous mutation, and (13.0%) c.470G>A (p.R157H)/c.470G>A (p.R157H) homozygous mutation. Biotinidase enzyme levels were found to be higher in patients with the p.D444H homozygous mutation than patients with other mutations. Biotin treatment was started in all patients with enzyme deficiency.
CONCLUSIONS
Since the treatment is inexpensive and easily available, it is vital to detect this disease before symptom onset, especially findings related to the central nervous system, hearing and vision loss. In patients diagnosed with enzyme deficiency, the diagnosis should be definitively confirmed by genetic analysis.
Topics: Biotinidase Deficiency; Child, Preschool; Female; Genotype; Humans; Infant; Infant, Newborn; Male; Mutation; Neonatal Screening; Phenotype; Retrospective Studies
PubMed: 34448386
DOI: 10.1515/jpem-2021-0242 -
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 -
AJNR. American Journal of Neuroradiology Mar 2023Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the gene. Resultant deficiency of free biotin leads to impaired activity of...
Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supplementation are critical. This practice is especially important in countries where routine neonatal screening for biotinidase deficiency is not performed. In this report comprising 14 patients from multiple centers, we demonstrate the MR imaging patterns of this disorder at various age groups. Knowledge of these patterns in the appropriate clinical context will help guide early diagnosis of this treatable metabolic disorder.
Topics: Infant, Newborn; Humans; Biotinidase Deficiency; Biotin; Biotinidase; Neonatal Screening; Neuroimaging
PubMed: 36759144
DOI: 10.3174/ajnr.A7781 -
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 Dec 2022Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral... (Review)
Review
Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral palsy. Early detection of these heterogenous genetic disorders can inform genetic counseling, anticipatory guidance, and improve outcomes, particularly where specific treatments exist. The diagnosis relies on clinical pattern recognition, biochemical testing, neuroimaging, and increasingly next-generation sequencing-based molecular testing. In this short review, we summarize the clinical and molecular understanding of: 1) childhood-onset and complex forms of hereditary spastic paraplegia (SPG5, SPG7, SPG11, SPG15, SPG35, SPG47, SPG48, SPG50, SPG51, SPG52) and, 2) the most common inborn errors of metabolism that present with phenotypes that resemble hereditary spastic paraplegia.
Topics: Child; Humans; Spastic Paraplegia, Hereditary; Phenotype; Retinal Degeneration; High-Throughput Nucleotide Sequencing; Metabolism, Inborn Errors; Mutation; Proteins
PubMed: 34183250
DOI: 10.1016/j.ymgme.2021.06.006