Sequence variants in the BTD underlying biotinidase deficiency in families of Pakistani origin

Authors

Tariq Moatter, Aga Khan UniversityFollow
Sibtain Ahmed, Aga Khan UniversityFollow
Hafsa Majid, Aga Khan UniversityFollow
Lena Jafri, Aga Khan UniversityFollow
Muhammad Bilal, Aga Khan University
Najum ud din, Hamdard University, Pakistan
Faisal Faisal, University of Sindh, Pakistan
Aysha Habib, Aga Khan UniversityFollow

Document Type

Article

Department

Pathology and Laboratory Medicine

Abstract

Background: Biotinidase deficiency (BTD) is a rare autosomal recessive metabolic disease, which develops neurological symptoms because of the impaired biotin recycling. Pathogenic mutations on BTD gene cause BTD deficiency. The clinical features and mutation analysis of Pakistani children with BTD deficiency have rarely been described. Herein, for the first time, we report the clinical features, BTD gene mutations and biochemical analysis of seven symptomatic children with BTD deficiency from Pakistan.
Methods: Seven suspected BTD-deficient patients who presented abnormal organic acid profiles and clinical features were subjected to Sanger sequencing to identify pathogenic mutations in the BTD gene. The results were analyzed by Mutation Surveyor Software.
Results: All seven patients exhibited common biotinidase deficiency symptoms including hypotonia, developmental delay and seizures. Biochemical analysis shows marked excretion of 3-hydroxy isovalerate in all cases, followed by 3-hydroxy propionate and methyl citrate. Sanger sequencing revealed one frame-shift mutation, c.98_104delinsTCC (p.Cys33Phefs), and two missense mutations, c.1612C>A (p.Arg538Ser) and c.1330G>C (p.Asp444His). All mutations were in the homozygous state and classified as pathogenic in published studies and mutation databases.
Conclusions: This study has validated the BTD variants as the underlying cause of biotinidase deficiency in which molecular testing of BTD is supported by urinary organic acid analysis and clinical diagnosis. Secondly, the strength of the local availability of this test in Pakistan will paved the way for the neonatal screening of biotinidase deficiency.

Comments

Pagination is not provided by the author/publisher.

Publication (Name of Journal)

The Journal of Gene Medicine

DOI

https://doi.org/10.1002/jgm.3597

Recommended Citation

Moatter, T., Ahmed, S., Majid, H., Jafri, L., Bilal, M., din, N. u., Faisal, F., Habib, A. (2023). Sequence variants in the BTD underlying biotinidase deficiency in families of Pakistani origin. The Journal of Gene Medicine, 26(1), e3597.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/1494