Comprehensive analysis of genotypic and phenotypic characteristics of biotinidase deficiency patients in the eastern region of Türkiye.

BACKGROUND

Biotin is a water-soluble vitamin that plays a key role in carboxylation. The formation of free biotin is impaired in biotinidase deficiency (BD), resulting in impaired biotin-dependent carboxylase functions. Based on the percentage of residual serum enzyme activity, BD is classified as partial and profound.

METHODS

Retrospective data including gender, age, parental consanguinity, family history, biotinidase activity analyses, type of deficiency (partial-profound), physical examination, treatment, and genotypes were evaluated in patients diagnosed with biotinidase deficiency in a single center in the eastern region of Türkiye. Patients whose biotinidase enzyme activity was below 30% with biallelic variants in the BTD gene were diagnosed as BD.

RESULTS

A total of 302 patients were included in the study. Parental consanguinity was present in 135 (44.7%) of them. Two hundred eighty-six (94.7%) were diagnosed by neonatal screening, 14 (4.6%) by family screening and two (0.06%) by clinical symptoms. Ninety-two (30.5%) of the patients were followed-up with profound deficiency and 210 (69.5%) with partial deficiency. A total of 306 variants were detected. Twenty different variants (3 novel - 3 rare) and 31 different genotypes were detected. The 3 most frequently detected variants were c.410G>A (p.Arg137His; 47.3%), c.1270G>C (p.Asp424His; 29.7%), and c.38_44delGCGGCTGinsTCC (p.Cys13Phefs36; 15.3%). The 3 most frequently identified genotypes were c.410G>A (p.Arg137His) / c.1270G>C (p.Asp424His) compound heterozygous (32.4%), c.410G>A (p.Arg137His) homozygous (24.8%), and c.38_44delGCGGCTGinsTCC (p.Cys13Phefs36) / c.1270G>C (p.Asp424His) compound heterozygous (12.2%). Patients with c.410G>A (p.Arg137His) homozygous variant, c.38_44delGCGGCTGinsTCC (p.Cys13Phefs36) homozygous variant and c.38_44delGCGGCTGinsTCC (p.Cys13Phefs36) / c.410G>A (p.Arg137His) compound heterozygous variant were statistically significantly associated with profound deficiency. Compound heterozygosity of c.410G>A (p.Arg137His) / c.1270G>C (p.Asp424His) variants were significantly associated with partial deficiency.

CONCLUSIONS

The association between the BTD genotype and biochemical phenotype is not always consistent. Our study provides valuable data by adding variants with genotype-phenotype correlations to the literature and three novel variants, which can provide significant guidance in clinical follow-up.