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

Autor:	Sürücü Kara İ; Department of Pediatric Metabolism, Ankara University, Faculty of Medicine, Ankara, Türkiye., Köse E; Department of Pediatric Metabolism, Ankara University Faculty of Medicine, Ankara University Rare Diseases Application and Research Center, Ankara, Türkiye., Koç Yekedüz M; Department of Pediatric Metabolism, Ankara University, Faculty of Medicine, Ankara, Türkiye., Eminoğlu FT; Department of Pediatric Metabolism, Ankara University Faculty of Medicine, Ankara University Rare Diseases Application and Research Center, Ankara, Türkiye.
Jazyk:	angličtina
Zdroj:	Journal of pediatric endocrinology & metabolism : JPEM [J Pediatr Endocrinol Metab] 2023 Sep 20; Vol. 36 (11), pp. 1061-1071. Date of Electronic Publication: 2023 Sep 20 (Print Publication: 2023).
DOI:	10.1515/jpem-2023-0337
Abstrakt:	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. (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu