Neurology
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
SeeTable 8.3. Neuroimaging. This should be urgent if there is reduced visual acuity (secondary to raised intracranial pressure), vomiting or headache. It should be avoided if the patient is areflexic and clinically has a peripheral neuropathy or telangiectasia in view of the chromosomal fragility in AT.CSF glucose to exclude glut-1 deficiency.Biotinidase.Nerve conduction studies to diagnose peripheral neuropathy and to distinguish from FA.Alpha-fetoprotein and immunoglobulins to screen for AT.White blood cell chromosome fragility (AT), DNA for genetic testing if a high index of suspicion of AT or FA; urine amino and organic acids, plasma amino acids; plasma and CSF lactate, biotinidase; phytanic acid; triglycerides and lipoproteins; white cell enzymes.
Nutrition Therapy of Inborn Errors of Metabolism
Fima Lifshitz in Childhood Nutrition, 2020
Biotinidase deficiency is another example of an inborn error of metabolism that is treated by supplementation cofactor, which in this case is biotin.26 Biotinidase cleaves biotin from holocarboxylases during metabolic degradation. The liberated biotin can then be reutilized. In patients with biotinidase deficiency, there is not adequate biotin present for the three mitochondrial biotin-dependent carboxylases propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, and pyruvate carboxylase. The patients present with hypotonia, seizures, skin rash, and alopecia. The urine contains metabolites, such as 3-hydroxyisovalerate, 3-methylcrotonylglycine, methylcitrate, 3-methylcrotonate, and 3-hydroxypro-pionate. Treatment involves supplementation of biotin in doses of 10 mg daily.
Pantothenic Acid and Biotin
Judy A. Driskell, Ira Wolinsky in Sports Nutrition, 2005
Biotinidase has one high-affinity and one low-affinity binding site for biotin and serves as a biotin-carrier protein in human plasma.22 In addition, albumin, α-globulin and β-globulin have affinity for biotin and may play a role in biotin transport in plasma.23 Evidence has been provided that 81% of the biotin in human plasma is free, 12% is covalently bound and 7% is reversibly bound.24 A biotin-binding glycoprotein (mol. wt. 66,000) is present in serum from pregnant female rats 25 but not in serum from male rats.23
Effect of perinatal biotin deficiency on auditory pathway of the Wistar-Albino rats
Published in Acta Oto-Laryngologica, 2019
Nevreste Didem Sonbay Yılmaz, Özer Erdem Gür, Nuray Ensari, Erdogan Bulut, Ozlem Tugce Kaya, Serap Sırvancı, Betul Danısman, Narin Derin, Bahri Gezgin, Nurdan Aygener, Mustafa Deniz Yılmaz
In a study by Heller et al. [6], biotinidase enzyme was shown to be widespread in the central nervous system. In the same study, biotinidase enzyme was found in the inner vibrating hair cells but not in the outer vibrating hair cells, and was extremely intense in the dorsal and ventral nuclei. It was also determined that the biotinidase enzyme concentration was greater in the inner vibrating hair cells than in other regions. This can be interpreted as there being a need for biotin for inner vibrating hair cell functions, whereas the functions of the outer vibrating hair cells are independent of biotin. The results of the current study suggest only partial agreement with this view. While there was no difference between the 4 groups of the current study in respect of the signal-nose ratios at 3000, 4000 and 6000 Hz in the DPOAE values, the ratios were higher in the B-N and B-B groups at 8000 and 10,000 Hz. These results were supported by the electron microscopy findings. In the B-N and B-B groups, deletions were determined in the stereocilia of the outer vibrating hair cells in the basal turn that are responsible for high frequency hearing. In the B-B group, these deletions extended to the mid turn. In the N-B group, the small amount of degeneration in the stereocilia of the outer vibrating hair cells in the basal turn was seen not to have affected the DPOAE results. Therefore, it can be considered that the functions of the outer vibrating hair cells are not independent of biotin and the outer vibrating hair cells in the basal turn that are responsible for hearing at high frequencies in particular are dependent on biotin.
Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns
Published in Expert Review of Molecular Diagnostics, 2018
David Millington, Scott Norton, Raj Singh, Rama Sista, Vijay Srinivasan, Vamsee Pamula
Thus far, the dialog has focused on LSD assays. In this section, we describe recent developments toward expanding the range of DMF to include other conditions that benefit from early identification through NBS. We reasoned that because several of the current assay methods in NBS programs are based on fluorometry for such conditions as biotinidase, hypothyroidism and galactosemia, for example, it would be logical to investigate the transfer of such assays to the DMF platform with a view toward simplifying the overall process of NBS. In another collaborative effort between Duke Health System Biochemical Genetics Laboratory, Advanced Liquid Logic and the North Carolina State Public Health Laboratory, a method to translate the NBS test for biotinidase was developed [54]. The enzymatic assay uses 4-methylumbelliferyl biotin, similar to a fluorogenic substrate currently used in benchtop NBS analyzers for biotinidase screening [55], as the fluorogenic substrate. Biotinidase deficiency assays were performed on Centers for Disease Control (CDC) proficiency test (PT) samples, and normal (n = 200) and deficient (n = 7) newborn DBS specimens using the same platform and extraction protocol, sample volumes, and incubation times as previously described for DMF-based LSD enzyme tests [14]. Enzymatic activity analysis of biotinidase deficiency revealed distinct separation between normal and affected DBS specimens using DMF (Figure 4) and PT results that matched the expected activity [55].
Neuro-Ophthalmic Literature Review
Published in Neuro-Ophthalmology, 2023
David A. Bellows, Noel C.Y. Chan, John J. Chen, Hui-Chen Cheng, Peter W MacIntosh, Collin McClelland, Michael S. Vaphiades, Konrad P. Weber, Xiaojun Zhang
There has been increasing recognition of genetic diseases that can cause magnetic resonance imaging (MRI) changes that mimic central nervous system (CNS) inflammatory disorders. While most of these manifest in childhood, there are some genetic diseases that can present in adulthood and cause significant diagnostic uncertainty. In this recent review in JAMA Neurology, Aryignac et al. discuss the most common adult-onset genetic diseases that can be confused with acquired neuroinflammatory disorders including genetic leukodystrophies, retinal vasculopathy with cerebral leukoencephalopathy (RVCL), Alexander’s disease, cytotoxic T-lymphocyte-associated protein haploinsufficiency, familial haemophagocytic lymphohistiocytosis, and biotinidase deficiency. Table 1 is especially helpful in summarising the MRI findings and suggestive features. Among these diseases, RVCL and biotinidase deficiency are the most likely to present in the neuro-ophthalmology clinic because their presenting symptom can be visual loss. RVCL is an autosomal dominant inflammatory microangiopathy caused by TREX1 gene mutations, which causes a vascular retinopathy, in addition to cognitive impairment, psychiatric symptoms, seizures, and focal neurological deficits. Biotinidase deficiency is an autosomal recessive disease that causes subacute bilateral optic neuropathy with central vision loss that can be accompanied by a myelopathy with longitudinal T2 lesions in the spinal cord.
Related Knowledge Centers
- Carboxylation
- Enzyme
- Lysine
- Protein
- Amino Acid
- Carbohydrate
- Gene
- Biocytin
- Biotin
- Fat