Rare diseases
The prevalence of the disease is estimated at:
The prevalence is generally higher in populations with a high rate of consanguinity (i.e., Turkey, Saudi Arabia) or in the Hispanic population. However, it seems lower in the African-American population.
Biotin (also known as vitamin H or B8) is an essential vitamin belonging to the vitamin B complex. Water soluble, biotin functions as a coenzyme for four carboxylases, essential for the proper functioning of gluconeogenesis, fatty acid synthesis and catabolism of various branched chain amino acids.
Biotinidase deficiency is a congenital error in biotin recycling metabolism. A deep biotinidase deficiency is defined as a residual activity < 10% of normal mean serum biotinidase activity, while a partial deficiency is defined as a residual activity between 10% and 30% of normal mean activity.
Young children with a profound biotinidase deficiency diagnosis usually develop symptoms of severe neurological abnormalities including convulsions, hypotonia, ataxia, psychomotor retardation, optic atrophy, sensorineural deafness and skin disorders (i.e., alopecia, rash, candidiasis). From a metabolic perspective, lactic acidosis with ketosis, organic aciduria and moderate hyperammonemia are possible. Later, weakness of the motor limbs and spastic paresis also develop. Visual, auditory, and neurological disorders are usually irreversible, even with treatment.
Individuals with partial biotinidase deficiency may suffer from symptoms of hypotonia, skin rashes and hair loss, particularly during periods of stress (i.e., prolonged infection, etc.).
The disease is caused by pathogenic variants in the BTD gene. These mutations are responsible for the absence or reduction of activity of biotinidase.
Biotinidase deficiency is demonstrated by a colorimetric assay that measures the release of p-aminobenzoic acid (p-ABA) from an artificial substrate, B-p-ABA or biotinyl-p-aminobenzoic acid. The lack of activity of biotinidase results in a lack of staining in the mentioned reaction.
The biotinidase deficiency diagnosis is confirmed by measuring its activity on plasma and possibly by measuring urinary organic acids. Finally, molecular sequencing of the BTD gene helps to bind the genotype. More than 150 pathogenic variants are described to date.
The treatment consists of daily vitamin supplements of biotin taken by mouth. This treatment is remarkably effective if started at a very early age. It prevents any clinical manifestation in subjects detected by neonatal screening and improves the clinical status of symptomatic patients. Once installed, however, some damage remains irreversible even under treatment with biotin, such as optic atrophy, deafness or developmental delay.
Biotin supplementation should be continued for life. This treatment has no known serious adverse effects. However, periodic ophthalmological, neurological and metabolic assessments are recommended.
Biotinidase deficiency is inherited in an autosomal recessive manner.
The NEONATAL Biotinidase Screening Assay kit is an enzymatic test for biotinidase activity quantification. This test is intended for neonatal screening of holocarboxylase or biotinidase (BTD) deficiency and is performed using dried blood samples on 903 or 226 blotting paper.