Biotinidase deficiency is a treatable autosomal-recessive metabolic disorder caused by biallelic pathogenic variants in BTD. Untreated profound deficiency can cause seizures, hypotonia, developmental delay, hearing and visual impairment, skin rash and alopecia.
Why it matters in epilepsy
Biotinidase deficiency is one of the classic treatable causes of early-life seizures.
Once diagnosed, lifelong pharmacological-dose biotin can prevent further metabolic episodes and, when started before symptoms, can allow normal development.
Profound and partial deficiency
Profound deficiency is defined by very low biotinidase activity and is associated with the most serious neurological complications if untreated.
Partial deficiency can produce milder symptoms, particularly during physiological stress such as prolonged infection.
Age at presentation
Symptoms in untreated profound deficiency can begin from the neonatal period through childhood, with a reported mean onset in infancy.
Seizure types
Seizures may be myoclonic, focal or generalised.
Infantile spasms have also been reported.
Other diagnostic clues
Features that should raise suspicion include eczema-like rash, alopecia, candidiasis, hypotonia, ataxia, hearing loss, optic atrophy and respiratory abnormalities.
Metabolic abnormalities
Untreated disease can produce ketolactic acidosis, organic aciduria and sometimes hyperammonaemia.
However, not every person has the full biochemical pattern during every episode.
Diagnosis
The key test is serum or plasma biotinidase enzyme activity.
Molecular testing of BTD can confirm the genetic cause.
Newborn screening
Biotinidase deficiency is included in newborn-screening programmes in many, but not all, countries.
People detected before symptoms and treated promptly are expected to develop normally.
Treatment
The treatment is lifelong oral biotin.
Seizures and hypotonia often improve after treatment begins.
What may not fully reverse
Hearing loss, optic atrophy and established developmental disability may persist if diagnosis was delayed.
This is why early recognition matters even when seizures later respond well.
Antiseizure medicines
Standard antiseizure medicines may be needed during acute presentation, but they do not correct the underlying metabolic defect.
Biotin is the disease-specific therapy.
Inheritance
Biotinidase deficiency is autosomal recessive.
If both parents are carriers, each pregnancy has a 25% chance of an affected child.
Worldwide access
Where newborn screening is absent, affected children may still present with unexplained epilepsy and multisystem symptoms.
The diagnostic enzyme assay is relatively simple compared with many rare metabolic tests, making awareness especially important.
The central point
Biotinidase deficiency is a treatable metabolic cause of epilepsy in which early biotin therapy can prevent permanent neurological disability.
Related reading
Metabolic Epilepsies →
Early Infantile DEE →
Sources
Medical note: biotinidase deficiency should be treated under metabolic specialist guidance; treatment is generally lifelong.
Evidence checked: September 2026.