Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency.

Biotin is an important water-soluble nutrient that aids in the metabolism of fats, carbohydrates, and proteins. Biotin deficiency can result in behavioral disorders, lack of coordination, learning disabilities, and seizures. Biotin supplementation can alleviate and sometimes totally stop such symptoms.

Signs and symptoms of a biotinidase deficiency (BTD) can appear several days after birth. These include seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death.^{[citation needed]}

Neonates with BTD may not exhibit any signs, and symptoms typically appear after the first few weeks or months of life. If left untreated, around 70% of infants with BTD will experience seizures (staring spells, jerking limb movements, stiffness, flickering eyelids), which often act as the first symptom of BTD. Infants with BTD may also have weak muscles and hypotonia; this may cause infants to appear abnormally "floppy" and have affected feeding and motor skills. BTD may result in developmental delays, vision or hearing problems, eye infections, alopecia, and eczema. The urine of infants with BTD may contain lactic acid and ammonia. Other symptoms that infants may exhibit include ataxia, breathing issues, lethargy, hepatomegaly, splenomegaly, and speech problems. The condition may eventually result in a coma and death.

Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period, they likely have some residual activity of biotin-related enzymes. Studies have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not exhibit symptoms until age 21. Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.

Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less. Individuals with partial biotinidase deficiency may have enzyme activity of 10–30%.

Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine.^{[citation needed]}

The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.