One of the essential vitamins is biotin, a cofactor for four enzymes with roles in intermediate metabolism. Biotin deficiency can be acquired: it can be due to inadequate biotin intake during parenteral nutrition, or due to consumption of raw egg white. Biotin deficiency can also be due to genetic defects in proteins that play an important role in biotin homeostasis.
Biotin deficiency can develop under a variety of circumstances. Within weeks to months, people on total parenteral nutrition lacking biotin, or infants fed on formula lacking biotin will start to display thinning or loss of hair and will develop scaly skin rashes, usually around the mouth, nose, and eyes. Similar symptoms develop in people who eat raw egg white for prolonged duration, which contains avidin, a protein that binds to biotin strongly. Neurological symptoms in adults include lethargy, depression, seizures, ataxia, and paresthesia of the hands and feet. Infants are also lethargic and have developmental problems. Other symptoms are acidosis and organic aciduria.
A milder form of biotin deficiency may develop because of increased catabolism of biotin. This may be caused by treatment with anticonvulsants  or by smoking . These are marginal effects, without the signs of overt deficiency. Pregnancy and lactation increase the demand for biotin  and thus, may also result in marginal biotin deficiency . However small degree of deficiency is also of crucial importance, as even marginal biotin deficiency can have teratogenic effects according to animal studies  . Chronic biotin deficiency may also develop in preterm infants fed on mother’s milk .
Biotin deficiency can also develop in people with genetic conditions affecting enzymes responsible for the metabolism of biotin . These include two vitamin transporters, which facilitate the movement of biotin into cells; a holocarboxylase synthetase, which binds biotin covalently to its target proteins; and biotinidase, which liberates free biotin from biotin containing peptides and biotinyl-lysine in the gastrointestinal system, and thereby plays a central role in the recycling and absorption of biotin. Biotinidase deficiency is an autosomal recessive condition. People with biotinidase defects present with symptoms similar to those of acquired biotin deficiency, but in addition have a hearing and vision loss  .
Bioassays have been developed and used for the determination of biotin levels in blood. However, plasma concentrations measured by these methods are often not reliable indicators of the biotin status, partly because the assays may not distinguish between biotin and its inactive metabolites . The secondary effects of biotin deficiency can be measured through assessing the activities of biotin-dependent enzymes  . Biotin is an essential cofactor for two acetyl-CoA carboxylases, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase . Decreased activity of methylcrotonyl-CoA carboxylase leads to the accumulation of methylcrotonyl-CoA and to its conversion to 3-hydroxyisovaleric acid, which can be measured in the urine. The concentration of 3-hydroxyisovaleric acid is a good indicator of the biotin status  .
Recently a new liquid chromatography tandem mass spectrometry method has been developed for the measurement of the carnitine-bound substrate/product pairs for the biotin-dependent enzymes . Thus, this method affords the determination of the activity of several biotin-dependent enzymes and therefore provides a more robust assessment of the biotin status in cases of marginal biotin deficiency (such as may occur in pregnancy) than assays relying on just one enzyme activity.
Biotidinase activity can be measured from blood samples on paper discs, or in serum using colorimetric assays. Children with less than ten percent of normal serum enzyme activity present with severe biotinidase deficiency .
Other tests may include urine ketone and organic acid levels, and serum ammonia levels.