Biotin is attached to the amino acid lysine within our body and in the food that we eat. Biotinidase detaches biotin from them and generates free biotin that can be attached to many enzymes, called carboxylases, and possibly used in other chemical reactions. Biotin is an essential cofactor for Acetyl-CoA, Propionyl-CoA, 3-Methylcrotonyl-CoA, and pyruvate carboxylase. None of these enzymes will work properly without biotin. In addition, biotin is essential for brain and nerve function.
The developing brain is particularly sensitive to biotin deficiency. Patients usually appear perfectly normal at birth, but can develop irreversible hearing and vision loss if untreated. With treatment, clinical outcomes are excellent. Without treatment, outcomes depend on the inherent severity of disease in the affected patient. In the severe form (profound biotinidase deficiency with enzyme activity <10% of normal), neurologic injury, seizures, hearing loss, blindness, and death may result. Symptoms may develop as soon as the first week of life or as late as 10 years of age (mean age of 3 1/2 months). The natural history and outcomes for untreated children with this disorder are only partially known. [Wolf: 2010]
Some children may have only one sign or symptom, others many. Initial signs/symptoms may include:
- hyperventilation, laryngeal stridor, and/or apnea
- eczematoid rash
Older children may manifest:
- limb weakness
- paresis and spasticity consistent with a myelopathy [Wiznitzer: 2003]
- developmental delay
- neurosensory hearing loss
- optic atrophy and scotomata
- recurrent viral and fungal infections
Children with untreated partial biotinidase deficiency (10-30% of normal enzyme activity) may manifest any of the above symptoms, though generally they will be mild and occur only with concomitant stressors, such as prolonged infection.
|Content Last Updated:||7/2012|
The authors listed above are responsible for the overall Biotinidase Deficiency Module. Authors contributing to individual pages in the module are listed on those pages.
Wiznitzer M, Bangert BA.
Biotinidase deficiency: clinical and MRI findings consistent with myelopathy.
Pediatr Neurol. 2003;29(1):56-8. PubMed abstract
Clinical issues and frequent questions about biotinidase deficiency.
Mol Genet Metab. 2010;100(1):6-13. PubMed abstract
Worldwide survey of neonatal screening for biotinidase deficiency.
J Inherit Metab Dis. 1991;14(6):923-7. PubMed abstract