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Biotin metabolism disorders and epilepsy Biotinase deficiency is caused by mutations in the gene encoding biotinase ( BTD gene), with 51% of cases attributed to the homozygous c.98-104del7ins3 mutation, It is an autosomal invisible genetic disorder with an estimated prevalence of about 1 in 60,000, and 20% of patients have a history of parental consanguinity [70]

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however, the combination had the strongest effects