Mutations in BTD causing biotinidase deficiency

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Biotinidase (BTD) is crucial for cleaving biocytin, a byproduct of holocarboxylase digestion.
• Profound BTD deficiency, an autosomal recessive disorder, can lead to severe neurological and cutaneous symptoms.
• The human BTD gene is located on chromosome 3p25, and its cDNA and genomic DNA have been characterized.

Purpose of the Study:

• To review and summarize the known mutations in the Biotinidase (BTD) gene.
• To analyze the frequency and distribution of BTD mutations in different patient populations.
• To explore potential genotype-phenotype correlations in BTD deficiency.

Main Methods:

• Literature review of reported BTD gene mutations.
• Analysis of mutation frequencies in symptomatic patients versus those identified through newborn screening.
• Examination of mutation data from diverse ethnic groups.

Main Results:

• 61 mutations in BTD exons and one intronic mutation causing profound deficiency have been identified.
• Specific mutations (98-104del7ins3, R538C) are prevalent in symptomatic patients.
• Other mutations (A755G, Q456H, 511 G>A; 1330G>C) are common in US newborn screening cases.
• Partial BTD deficiency is often linked to the 1330G>C mutation (D444H).
• Preliminary findings suggest a lack of clear genotype-phenotype correlation, despite a prevalence of mutations yielding truncated BTD protein.

Conclusions:

• Numerous mutations in the BTD gene cause profound and partial deficiency.
• Mutation frequencies differ between symptomatic individuals and those detected via newborn screening.
• Further research is needed to establish definitive genotype-phenotype correlations in Biotinidase deficiency.