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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 -
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 -
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 -
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 -
Expert Review of Endocrinology &... Nov 2008Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of...
Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role in transcriptional repression of genes and genome stability. Biotin deficiency may be caused by insufficient dietary uptake of biotin, drug-vitamin interactions and, perhaps, by increased biotin catabolism during pregnancy and in smokers. Biotin deficiency can also be precipitated by decreased activities of the following proteins that play critical roles in biotin homeostasis: the vitamin transporters sodium-dependent multivitamin transporter and monocarboxylate transporter 1, which mediate biotin transport in the intestine, liver and peripheral tissues, and renal reabsorption; holocarboxylase synthetase, which mediates the binding of biotin to carboxylases and histones; and biotinidase, which plays a central role in the intestinal absorption of biotin, the transport of biotin in plasma and the regulation of histone biotinylation. Symptoms of biotin deficiency include seizures, hypotonia, ataxia, dermatitis, hair loss, mental retardation, ketolactic acidosis, organic aciduria and also fetal malformations. This review focuses on the deficiencies of both biotin and biotinidase, and the medical management of such cases.
PubMed: 19727438
DOI: 10.1586/17446651.3.6.715 -
Orphanet Journal of Rare Diseases Jan 2019Biotinidase deficiency is an autosomal recessive disorder that affects the endogenous recycling and release of biotin from dietary protein. This disease was thought to...
Biotinidase deficiency is an autosomal recessive disorder that affects the endogenous recycling and release of biotin from dietary protein. This disease was thought to be rare in East Asia. In this report, we delineate the phenotype of biotinidase deficiency in our cohort. The genotypes and phenotypes of patients diagnosed with biotinidase deficiency from a medical center were reviewed. The clinical manifestations, laboratory findings, and molecular test results were retrospectively analyzed. A total of 6 patients were evaluated. Three patients (50%) were diagnosed because of a clinical illness, and the other three (50%) were identified by newborn screening. In all patients, the molecular results confirmed the BTD mutation. The three patients with clinical manifestations had an onset of seizure at the age of 2 to 3 months. Two patients had respiratory problems (one with apnea under bilevel positive airway pressure (BiPAP) therapy at night, and the other with laryngomalacia). Hearing loss and eye problems were found in one patient. Interestingly, cutaneous manifestations including skin eczema, alopecia, and recurrent fungal infection were less commonly seen compared to cases in the literature. None of the patients identified by the newborn screening program developed symptoms. Our findings highlight differences in the genotype and phenotype compared with those in Western countries. Patients with biotinidase deficiency benefit from newborn screening programs for early detection and management.
Topics: Asian People; Biotinidase Deficiency; Genotype; Humans; Infant, Newborn; Mutation; Neonatal Screening; Phenotype; Retrospective Studies
PubMed: 30616616
DOI: 10.1186/s13023-018-0992-2 -
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 -
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