Biotin deficiency leads to many clinical abnormalities, mainly neurological and dermal abnormalities. History includes recognizing risk factors for biotin deficiency, such as history related to gastrointestinal disease or inflammatory bowel disease. Any history of drug intake that interferes with biotin metabolism or uptake is significant, e.g., antiepileptics, antibiotics, or isotretinoin. Dermal abnormalities in biotin deficiency are due to impaired fatty acid metabolism. These include hair loss (alopecia) and periorificial dermatitis; scaly, red rash around the orifices, i.e., eyes, nose, and mouth (also called “biotin-deficient face”). The rash is similar to that of zinc deficiency. Patients may also develop conjunctivitis and skin infections.

Neurological symptoms include hypotonia, seizures, ataxia, numbness, and tingling of the extremities, mental retardation, and developmental delay in children. The patient may show depression, lethargy, and a history of hallucinations. Other biotin deficiency presentations include ketolactic acidosis and organic aciduria. Individuals with hereditary disorders of biotin deficiency such as biotinidase deficiency may also show impaired immune system function leading to increased susceptibility to infections, e.g., Candida. Biotinidase deficiency typically shows symptoms at the age of 1 week to more than one year and may have additional symptoms like hearing loss and optic atrophy.

As observed in swine, initial clinical symptoms of acquired biotin deficiency include gradual onset of hair loss, dry skin, and lesions on the feet and legs after six months of biotin deficiency. After nine months, the clinical picture resembles a characteristic cutaneous lesion of biotin deficiency. In human adults, after 3 to 4 weeks of having a raw egg diet, desquamative dermatitis was observed. After five weeks, anorexia, lethargy, and hyperaesthesia developed. Administration of biotin relieved symptoms in 5 days. Infants may initially show mild scaly erythema and dermatitis on face, particularly malar prominences which may resemble dermatitis rash due to soaps.

The diagnostic tests for biotin deficiency are urinary 3-hydroxyisovaleric acid and biotin, and the status of propionyl-CoA carboxylase in lymphocytes.[8][9] Biotin-dependent carboxylases in human lymphocytes are reliable markers for determining biotin status. Decreased activity of beta-methylcrotonyl-CoA carboxylase shunts the catabolism to alternative pathways, leading to the elevated formation of 3-hydroxyisovaleric acid. The most reliable marker of biotin deficiency is increased excretion of 3-hydroxyisovaleric acid in the urine (over 195 micromol/24 hours). Evidence shows that serum biotin concentration does not decrease in biotin deficiency patients who are receiving biotin-free total parenteral nutrition. Therefore, serum biotin levels are not reliable indicators of marginal biotin deficiency.[5][8] If biotin deficiency is suspected, it warrants a thorough neurological examination and other investigations, including vision and hearing testing.

Biotinidase deficiency confirmation is done by DNA analysis, either allele-targeted methods or full-gene sequencing. Currently, all newborn screening programs in the U.S. and more than 30 other countries carry out screening for biotinidase deficiency.[6][7]

Biotin deficiency management essentially means treating the cause. Oral biotin supplements have high bioavailability. Usually, a dose of 5 mg/day is given regardless of the etiology of biotin deficiency.[5] The Food and Nutrition Board of the National Research Council recommends a range of 5 mcg/day in newborn infants, to 35 mcg/day in lactating women.

Practitioners should be aware that biotin requirements may increase during anticonvulsant therapy [8]. In biotinidase deficiency, patient therapy typically consists of lifelong doses of biotin. Biotin doses in the range of 5 to 20 mg can treat and prevent clinical signs and symptoms of biotinidase deficiency.[7][9]

The significant differential includes the inborn error of metabolism such as sodium-dependent multivitamin transporter defect. Sodium-dependent multivitamin transporter defect can cause a metabolic disorder similar to biotinidase deficiency. There is a deficiency of biotin, pantothenic acid, and lipoate.[11] Biotin deficiency can present with a clinical picture similar to that of acrodermatitis enteropathica (a disorder of zinc metabolism). 

Biotin deficiency can present with symptoms similar to zinc deficiency. Biotin is necessary for zinc homeostasis in the skin; the precise nature of this association between zinc and biotin is unknown.[3] The clinician can differentiate zinc deficiency skin rash from biotin deficiency rash as zinc deficiency causes bullous, scaly (scald like) lesions on facial orifices as well as friction areas of the body. Zinc deficiency causes angular cheilitis, alopecia, and paronychia.[12]

Biotin deficiency is rare and has a relatively good prognosis. Children diagnosed with biotinidase deficiency require early intervention and life-long biotin treatment. Children who quit therapy develop symptoms again within weeks to months. When neonates diagnosed by neonatal screening receive biotin, they develop normally without having any symptoms, and those with symptoms respond quickly to biotin treatment. Failure to evaluate and manage biotinidase deficiency at an early stage can cause irreversible neurodevelopmental abnormalities and can lead to developmental delay and autistic behavior.[6][7][9] 

Since biotin plays a crucial role in maintaining the cell-mediated and humoral immunity, biotin deficiency due to inborn errors of metabolism can cause candidiasis of the skin in infants and children. There may be IgA deficiency and low percentages of T lymphocytes. They may have absent delayed-hypersensitivity skin-tests responses.

Biotin deficiency can cause encephalopathies. Patients usually respond well to large doses of biotin. Evidence shows that a lack of biotin is teratogenic in animal models. Strains of mice with biotin deficiency developed fetal malformations, most commonly cleft palate, micrognathia, and micromelia.[8][9][13][14]

Marginal biotin deficiency is common in pregnancy and may be due to an increased demand for biotin. Likewise, lactation can lead to an increased demand for biotin.[8] Clinical data shows that patients of multiple sclerosis, when treated with daily biotin doses of up to 300 mg, respond positively, with a reversal in disease progression as well as reduce chronic disability.[1][2] The likely mechanism is due to increased myelin production leading to increased axonal remyelination. Biotin may also increase energy production and hence decrease axonal hypoxia in multiple sclerosis.[2]

Biotin deficiency occurs in severely malnourished children in the developed world, thus creating a global public health problem. Biotinidase screening should be part of the workup of infants or children showing clinical features of the disease; it is a routine part of neonatal screening in many countries.[7][9] Management of the disorder is optimally by a pediatrician, endocrinologist, and a geneticist. Both nursing and pharmacists should educate parents about the appropriate dosage and the need for compliance, and not stop taking supplemental biotin unless they are told to stop by their clinician. A dietician or nutritionist may also be part of the management team in the rare instances where dietary insufficiency is the etiology. All these disciplines need to function as an interprofessional healthcare team to manage biotin deficiency and guide the patient to an optimal outcome. [Level V]

Biotin supplements are readily available in the market. It is routinely given as a nutritional supplement for the treatment of hair loss and brittle nails. Evidence demonstrates the effectiveness of biotin supplements in splitting brittle nails (onychoschizia, onychoschisis). However, not much evidence favors the use of biotin supplementation in hair loss unless it is due to hereditary abnormalities of biotin metabolism or acquired biotin deficiency.[5] Health professionals should take this information into account and educate the patients. A dietary consult is recommended as patients need to know the type of food rich in biotin.

The primary care clinicians need to follow these patients, as it often takes months to reverse the symptoms. For patients who remain compliant with treatment, the outcomes are good.