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

İlknur Sürücü Kara; Engin Köse; Merve Koç Yekedüz; Fatma Tuba Eminoğlu

doi:10.1515/jpem-2023-0337

Article

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

İlknur Sürücü Kara , Engin Köse , Merve Koç Yekedüz and Fatma Tuba Eminoğlu

Published/Copyright: September 20, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 36 Issue 11

Abstract

Objectives

In the present study, we aimed to evaluate the genotype-phenotype relation in patients with biotinidase enzyme deficiency based on repeated biotinidase enzyme measurements.

Methods

The hospital file information of patients with biotinidase, enzyme deficiency was assessed retrospectively, and the relationship between the BTD gene mutations analysis results and biotinidase enzyme activity following the first and repeated enzyme activity assessments was analyzed.

Results

One-hundred-ten patients were included. In the first enzyme evaluation, profound biotinidase enzyme deficiency was identified in 15 (13.6 %), partial biotinidase enzyme deficiency in 63 (57.3 %), and heterozygous biotinidase enzyme deficiency in 32 (29.1 %) of the patients. The BTD genetic analysis revealed 42 (38.2 %) homozygous, 42 (38.2 %) heterozygous, and 26 (23.6 %) compound heterozygous variants. The most common homozygous variant, p.Asp444His, was evaluated with 130 repeated enzyme measurements and was consistent with a partial biotinidase enzyme deficiency in 55.4 % of cases, heterozygous biotinidase enzyme deficiency in 43.8 % of cases, and profound biotinidase enzyme deficiency in one (0.8 %) case. Clinical symptoms developed in 17 patients during follow-up, of which 70.6 % were related to neurodevelopment. The most common variant was homozygous p.Asp444His (29.4 %) among the patients who developed symptoms.

Conclusions

This is the first study to date to evaluate the genotype-phenotype relationship in patients with biotinidase deficiency through repeated measurements of biotinidase enzyme activity. The study reveals that biotinidase enzyme activity alone is inadequate for diagnosing biotinidase enzyme deficiency or evaluating disease severity, as genetic investigations are also required for a definitive diagnosis of biotinidase enzyme deficiency.

Keywords: biotinidase enzyme activity; BTD gene; p.Asp444His variant; repeated measurement

Corresponding author: Engin Köse, MD, Department of Pediatric Metabolism, Ankara University Faculty of Medicine, Ankara University Rare Diseases Application and Research Center, Cebeci Campus, Children’s Hospital, 06620, Balkiraz Street, Mamak, Ankara, Türkiye, Phone: +90 505 271 96 19, Fax: +90 312 595 64 02, E-mail: enginkose85@hotmail.com

Research ethics: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ankara University Faculty of Medicine Clinical Research Ethics Committee (approval number: 2023000245-1(2023/245)).
Informed consent: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2023-07-17

Accepted: 2023-09-02

Published Online: 2023-09-20

Published in Print: 2023-11-27

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https://doi.org/10.1515/jpem-2023-0337

Keywords for this article

biotinidase enzyme activity; BTD gene; p.Asp444His variant; repeated measurement