Btd, encoding biotinidase, is the sole enzyme capable of cleaving biocytin, a product from the proteolytic digestion of holocarboxylases. This function is crucial for biotin recycling, and its deficiency can disrupt biotin-dependent carboxylase functions, with potential impacts on various biological processes [1].

Mutations in the Btd gene cause biotinidase deficiency, an autosomal recessive disorder. Profound deficiency (less than 10% mean normal activity in serum) can lead to neurological and cutaneous abnormalities. Different mutations have been identified in symptomatic children and those detected by newborn screening. For example, mutations 98-104del7ins3 and R538C were prevalent in symptomatic patients, while A755G, Q456H, and 511 G>A; 1330G>C (double mutation) were common in newborn screening in the US [1]. Partial deficiency (10-30% of mean normal serum activity) often results from the 1330G>C mutation in combination with another profound-deficiency-causing mutation [1]. In addition, studies on different Btd gene variants in vitro showed varied impacts on biotinidase activity, with some variants being deleterious, some related to a milder phenotype, and some not deleterious [2]. Also, in Pakistani children with biotinidase deficiency, specific mutations in Btd were identified, validating its role in the disorder [3].

In conclusion, Btd is essential for biotin recycling, and its deficiency can lead to significant health issues. Understanding the role of Btd through genetic studies, especially those identifying mutations causing deficiency, helps in diagnosing and potentially managing biotinidase-deficiency-related diseases.