Biotinidase deficiency is a rare genetic disorder that affects the body's ability to recycle and reuse biotin, a water-soluble B vitamin. This deficiency is caused by mutations in the BTD gene, which provides instructions for producing the biotinidase enzyme. The prevalence of biotinidase deficiency is estimated at 1 in 61,000 individuals, and the frequency of carriers in the general population is approximately 1 in 120 people.
Biotinidase deficiency genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Key features of Biotinidase Deficiency include:
- Biotin Recycling Impairment: Biotinidase is essential for recycling biotin, a crucial vitamin in various metabolic processes. When biotinidase is deficient, the body cannot effectively recycle and reuse biotin.
- Symptoms of Biotin Deficiency: Without sufficient biotin, various enzymes essential for metabolic functions become impaired. Symptoms may include skin rash, hair loss, seizures, developmental delays, hypotonia (low muscle tone), and neurological abnormalities.
- Age of Onset: Symptoms of biotinidase deficiency can manifest at different ages. In some cases, symptoms may appear during infancy or early childhood.
- Severity Spectrum: Symptoms can vary widely, ranging from mild to profound. Early and severe forms may lead to significant neurological complications if not treated promptly.
- Newborn Screening: Many countries often include Biotinidase deficiency in newborn screening programs. Early detection through newborn screening allows for early intervention and treatment, preventing or minimizing the development of symptoms.
- Treatment with Biotin Supplementation: The mainstay of treatment for biotinidase deficiency is the administration of biotin supplements. Biotin supplementation helps compensate for the lack of recycling and ensures the availability of biotin for essential metabolic processes. Lifelong biotin supplementation is typically required to manage the condition effectively. Regular monitoring of biotin levels and ongoing medical care are important components of long-term management.
Genetic counseling is recommended for families affected by biotinidase deficiency. Understanding the inheritance pattern and assessing the risk for future generations is essential.
Early diagnosis and prompt initiation of biotin supplementation are crucial for preventing or minimizing the development of symptoms and complications associated with biotinidase deficiency. Regular follow-up and adherence to prescribed treatment plans contribute to optimal outcomes for individuals with this condition.
Biotinidase deficiency, caused by pathogenic variants in BTD, follows an autosomal recessive mode of inheritance. More than 200 variants associated with this syndrome have been identified. Those variants that cause a total or near-total loss of biotinidase function when in homozygosis (two copies of the same variant) or compound heterozygosis (two copies of different pathogenic variants on different chromosomes) result in profound BTD deficiency.
Five mutations account for approximately 60% of the alleles found in symptomatic individuals or were identified by neonatal screening: c.98_104del7ins3, c.1308A>C, c.1552C>T, c.1330G>C, and c.451G>A.
The c.1552C>T variant has been reported in both homozygosis and compound heterozygosis cases of profound deficiency. Affected patients show very low serum biotinidase activity (below 10%).
The c.1330G>C variant causes a decrease in enzyme activity, reducing plasma biotin levels by 50%. It has been found in patients in homozygosis and compound heterozygosis, for example, combined with c.451G>A.
On the other hand, one of the most common variants, present in 28% of those affected and causing profound biotinidase deficiency, is c.1308A>C.
The genetic test of Biotinidase deficiency analyzes the 19 most frequent pathogenic mutations of the BTD gene.
With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).
