The Course of Biotinidase Activities After Neonatal Period in The Screened Newborns and Consequences of The Concordance With Their Genotypes.

Abstract

Background/aim: Biotinidase deficiency (BTD) is characterized by broad genotypic variants and unsteady biotinidase activity. Increasing enzyme activity and maturation throughout childhood. This study aims to reveal the course of biotinidase activities in a long-term follow-up period and concordance with their genotypes .Participants/Methods: A total of 1,773 biotinidase enzyme (BT) activity measurements were performed in 711 newborns with variants in the BTD gene over a 4-year follow-up period. Biochemical phenotyping was classified into four groups based on the highest measured enzyme activity level during the follow-up: Profound(≤10%), Partial(10.1-30%), Heterozygous(30.1-66.5%), and Normal(>66.6%). Results: The number of participants with BTD in the biochemical phenotype groups assigned based on the first measurement was 59, 217, 314, and 121 in the profound, partial, heterozygous, and normal groups respectively. Based on the highest measurement value during follow-up, the number and net changes of participants in groups were 22(-37), 95(-122), 333(+19), and 261(+140), respectively. The overall concordance between genotypes and biotinidase activities based on the highest measurement was 50.7%. A moderate correlation was found between the highest enzyme value and age (r=-0.573, p=0.002) in heterozygous plus normal biochemical phenotype groups in first months.Conclusion:This study shows that the biotinidase activities increase at a later age after neonatal period during long-term follow-up, and there is low concordance between the biochemical phenotype and their genotype. These findings indicate the important role of the monitoring the course of biotinidase enzyme activities for a longer period of time to determine the treatment decision.

A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity

“…[2] There have been many studies to date evaluating the relationship between genotypes and phenotypes in biotinidase enzyme de ciency, however biotinidase enzyme activity measurements were made only once or twice in most of them. [2][3][4][5][6][7][8][9][10][11][12][13] As biotinidase enzyme activity measurements may be affected by such external factors as age, prematurity, neonatal jaundice and the temperature of the sample during storage or transport, [1; 4; 14; 15] it is suggested that a diagnosis of biotinidase enzyme de ciency should be based on multiple measurements of plasma biotinidase enzyme activity. [4] We believe that repeated measurement of biotinidase enzyme activity during the clinical follow-up of patients with biotinidase enzyme de ciency can lead to a better evaluation of the genotype and phenotype relationship and the exclusion of external factors.…”