Recovery of enzyme activity in biotinidase deficient individuals during early childhood. Issue 3 (3rd March 2022)

• Record Type: Journal Article
• Authors: Forny, Patrick; Wicht, Andrea; Rüfenacht, Véronique; Cremonesi, Alessio; Häberle, Johannes
• Is Part Of: Journal of inherited metabolic disease. Volume 45:Issue 3(2022)
• Page Start: 605
• Page End: 620
• Publication Date: 2022-03-03
• Subjects: biotin therapy -- biotinidase deficiency -- biotinidase enzyme activity -- BTD variants -- newborn screening; Metabolism, Inborn errors of -- Periodicals; Metabolism -- Disorders -- Periodicals; 616.39042
• DOI: 10.1002/jimd.12490
• Languages: English
• ISSNs: 0141-8955

Abstract

Abstract: Deficiency of the biotinidase (BTD) enzyme is an inborn error of biotin metabolism caused by biallelic pathogenic variants in the BTD gene. There are two forms, partial and profound BTD deficiency, which both can be successfully treated with pharmacological doses of biotin, justifying the inclusion of this disorder in the newborn screening in numerous countries. We investigated the BTD deficiency cohort ( N = 87) in our metabolic center, as it was detected upon newborn screening since 2005, and aimed to better understand the long‐term course of BTD enzyme activity and how it may relate to the patients' genetic background. We observed that individuals with partial BTD deficiency display an elevation of BTD enzyme activity with increasing age in 48% of cases—a recovery which allowed adjustment or stop of biotin supplementation in 20% of all individuals. In addition, we were able to recruit 56 patients (64%) for genetic testing, revealing 19 different variants (2 novel), and constituting 22 different genotypes. Genotype–phenotype correlations revealed that the most abundant allele in our cohort p.(Asp444His) was also the most common variant in patients displaying recovery of BTD enzyme activity. Based on our results, we recommend to retest all patients with partial BTD deficiency at the age of 5 years, as this may result in an impact on therapy. Moreover, genetic testing of BTD deficient individuals can allow prediction of the severity of BTD deficiency and of the likelihood of BTD enzyme activity recovery with age.