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 [1] or by smoking [2]. These are marginal effects, without the signs of overt deficiency. Pregnancy and lactation increase the demand for biotin [3] and thus, may also result in marginal biotin deficiency [4]. However small degree of deficiency is also of crucial importance, as even marginal biotin deficiency can have teratogenic effects according to animal studies [4] [5]. Chronic biotin deficiency may also develop in preterm infants fed on mother’s milk [6].

Biotin deficiency can also develop in people with genetic conditions affecting enzymes responsible for the metabolism of biotin [7]. 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 [7] [8].

• Pain

  Muscle Pain - Deep rooted muscle pain, nerve pain and cramps have all been associated with a lack in vitamin B7, this is thought to be because of the relationship between the vitamin and the metabolic process. [healthyhairplus.com]

  Here are signs that suggest biotin deficiency: Nerve pain: Numbness, tingling, prickly sensations, pain or any other "paresthesia." It can occur by itself, or as part of kidney disease, insulin resistance or diabetes. [gainesville.com]

  […] periorofacial macular rash Seborrheic dermatitis Fungal infections Fine and brittle hair Hair loss or total alopecia Mild depression, which may progress to profound lassitude and, eventually, to somnolence Changes in mental status Generalized muscular pains [medicowesome.com]

  Symptoms of deficiency Hair loss Dry, scaly skin Cracked lips Swollen and painful tongue Dry eyes Loss of appetite Fatigue Insomnia Depression. [justvitamins.co.uk]

  Hallucinations. 1, 5 Heart function impairment. 3, 8 Increased number of bacterial and fungal infections due to impaired immunity. 3, 5 Insomnia. 3 Leiner's disease. 4 Loss of appetite. 3 Loss of hair color. 1 Loss of hearing. 10 Mental retardation. 7 Muscle pain [biotin.com]

• Developmental Delay

  Investigation of global developmental delay. Arch Dis Child 2006;91:701–5. [bestbets.org]

  Each patient had alopecia totalis, hypotonia, and developmental delay. Two developed the characteristic scaly periorificial dermatitis; one had only an intermittent scaly rash on the cheeks and occipital scalp. [ncbi.nlm.nih.gov]

  Even when restricting the patient population to those suffering from developmental delay, screening is not justified. [ 11 ] [patient.info]

  Dermatitis, microcephaly, developmental delay and convulsions were observed. The patients with partial BD did not have any clinical symptoms except one sibling with borderline IQ score. None of the parents was symptomatic. [doi.org]

  Symptoms of biotin deficiency vary widely because biotin is involved in so many biochemical processes in the body. 4 Clinical signs may include: Anemia. 3 Ataxia. 7 Depression. 1, 5 Developmental delays. 18 Elevated cholesterol levels. 3 Fatigue. 1, 5 [biotin.com]

• Anemia

  Anemia Biotin deficiency may cause slight anemia. This condition causes oxygen-carrying cells called hemoglobin to lose their ability to bind oxygen. [fitday.com]

  Anemia: The hemoglobin cells lose their ability to tote oxygen, leaving you feeling winded, short of breath, inattentive and fatigued with little exertion. Prolonged anemia raises risk for heart failure. [gainesville.com]

  Pathogenesis Excess consumption of raw egg whites, which are rich in avidin, an egg-white protein that chelates biotin. biotin deficiency Clinical nutrition A condition caused by a lack of biotin characterized by anemia, dry skin, enteritis, and hypercholesterolemia [medical-dictionary.thefreedictionary.com]

  which is characterized by megaloblastic anemia. [podiatrytoday.com]

  Anemia Deficiency of vitamin B leads to poor metabolism and growth. [newsmax.com]

• Weakness

  Investigation of potential mechanisms provides evidence that biotin transport by the human placenta is weak. [ncbi.nlm.nih.gov]

  Leg weakness. Scabs around eyes and beak. Thickened skin under foot pad, in embryos, webbing between toes. Chondrodystrophy. Sudden deaths in fatty liver and kidney syndrome. Post-mortem lesions See signs. [thepoultrysite.com]

  Heart function impairment. 3, 8 Increased number of bacterial and fungal infections due to impaired immunity. 3, 5 Insomnia. 3 Leiner's disease. 4 Loss of appetite. 3 Loss of hair color. 1 Loss of hearing. 10 Mental retardation. 7 Muscle pain. 3 Muscle weakness [biotin.com]

  Sounds like a dream right, but it can actually contribute to depression, lethargy and weakness. [gainesville.com]

  Symptoms of biotin deficiency include; hair loss, red scaly rash around the nose, mouth and genital area, brittle nails, Candida dermatitis, unusual odour to the urine, immune deficiencies and muscle weakness. [kingswaycompounding.com.au]

• Anorexia

  Anorexia Anorexia is a condition that causes a person to suffer from low appetite. Biotin deficiency in infants hinders their physical and mental growth. [fitday.com]

  Hair loss or total alopecia Mild depression, which may progress to profound lassitude and, eventually, to somnolence Changes in mental status Generalized muscular pains (myalgias) Hyperesthesias and paresthesias N ausea, occasionally severe Vomiting Anorexia [medicowesome.com]

  Deficiency Symptoms: Symptoms of biotin deficiency include erythematous exfoliative dermatitis, thinning hair, fatigue, irritability, mild depression, somnolence, muscle pains, anorexia, nausea, mild anemia. [info.spectracell.com]

  Anorexia: You're not hungry if you have biotin deficiency. Sounds like a dream right, but it can actually contribute to depression, lethargy and weakness. [gainesville.com]

  […] including red, patchy ones near the mouth (erythematous periorofacial macular rash) Fine and brittle hair Hair loss or total baldness (alopecia) Anemia Birth defects (still being studied) Seborrheic dermatitis Fungal infections Hallucinations Lethargy Anorexia [en.wikipedia.org]

• Loss of Appetite

  Symptoms of deficiency Hair loss Dry, scaly skin Cracked lips Swollen and painful tongue Dry eyes Loss of appetite Fatigue Insomnia Depression. [justvitamins.co.uk]

  […] and thinning hair. 1, 7 Hallucinations. 1, 5 Heart function impairment. 3, 8 Increased number of bacterial and fungal infections due to impaired immunity. 3, 5 Insomnia. 3 Leiner's disease. 4 Loss of appetite. 3 Loss of hair color. 1 Loss of hearing. [biotin.com]

  The symptoms of biotin deficiency include scaly skin, brittle nails, thinning hair, dry eyes, fatigue, loss of appetite, depression and cracks in the corners of the mouth. [livestrong.com]

  Dietary symptoms include fatigue, dry skin, body hair loss, nausea, loss of appetite and mild depression. [info.spectracell.com]

  Signs and Symptoms Deficiency symptoms include anemia, chronic fatigue, loss of appetite, impairment of fat metabolism, irregular heartbeat, impaired cognitive skills, anorexia, baldness, alopecia, insomnia, depression, drowsiness, hallucinations, muscle [diagnose-me.com]

• Muscle Cramp

  A proper supplement of biotin may reduce muscle cramps in kids. 2. [fitday.com]

• Muscle Hypotonia

  Chief characteristics include weak muscles (hypotonia), seizures, hair loss (alopecia), an inflammatory skin rash (eczema), developmental delays, and lactic aciduria. [rarediseases.org]

• Dermatitis

  Candida infections secondary to impaired immune function might also contribute to the dermatitis of biotin deficiency. [ncbi.nlm.nih.gov]

  Noah Scheinfeld, Diaper Dermatitis, American Journal of Clinical Dermatology, 10.2165/00128071-200506050-00001, 6, 5, (273-281), (2005). Emily L. Kazaks and Alfred T. Lane, DIAPER DERMATITIS, Pediatric Clinics of North America, 47, 4, (909), (2000). [doi.org]

  Dermatitis Skin inflammation is one of the common symptoms of biotin deficiency. The common form of dermatitis that is found in people who are suffering from biotin deficiency is seborrhoeic dermatitis. [fitday.com]

• Alopecia

  Each patient had alopecia totalis, hypotonia, and developmental delay. Two developed the characteristic scaly periorificial dermatitis; one had only an intermittent scaly rash on the cheeks and occipital scalp. [ncbi.nlm.nih.gov]

  The boy presented with perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. [en.wikipedia.org]

• Skin Rash

  After biotin supplementation, the skin rash improved and biotinidase activity normalized. We speculate that biotin is one regulating factor in the biosynthesis of biotinidase. [ncbi.nlm.nih.gov]

  Biotin mnemonic Symptoms of deficient biotin intake are: Dry skin Rashes, including erythematous periorofacial macular rash Seborrheic dermatitis Fungal infections Fine and brittle hair Hair loss or total alopecia Mild depression, which may progress to [medicowesome.com]

  Without treatment, affected children may experience hypotonia, skin rashes, and hair loss, but these problems may appear only during illness, infection, or other times of stress. [ghr.nlm.nih.gov]

  Experts say gray and thinning hair could be a symptom of biotin deficiency. ( 1 ) Numbness, burning, and tingling in arms, legs, hands, and feet. 1, 3, 5 Pallor. 3 Red and scaly skin rash (around eyes, mouth, nose, and genitals); usually tests positive [biotin.com]

  Due to improper fat metabolism, one can develop acne, dry itchy skin, erythematous rash on the face and body. [durablehealth.net]

• Eczema

  Chief characteristics include weak muscles (hypotonia), seizures, hair loss (alopecia), an inflammatory skin rash (eczema), developmental delays, and lactic aciduria. [rarediseases.org]

  These can be seen alone or in combination with eczema, psoriasis and dandruff. The belief for symptoms presenting in this manner is also closely linked to the integral part biotin plays in the metabolic process. [healthyhairplus.com]

  Skin conditions: Eczema, psoriasis, seborrheoeic dermatitis, flaking, itching, scaly, dry or inflamed skin, sores in or around the mouth, burning mouth/tongue, all of these problems suggest biotin (or another B vitamin) deficiency. [gainesville.com]

  Biotin is used not only to improve the quality of hair, but also for the treatment of acne, brittle nails, diabetes, eczema and dermatitis. The major job of biotin is to renew the roots of the already grown hair. [vitaminsforhairguide.com]

  It's commonly used to remediate neurological problems, hair loss (alopecia) and skin conditions (such as acne and eczema) associated with a lack of certain enzymes. [articles.mercola.com]

• Eruptions

  Calobrisi, Skin eruptions in the diaper area, Current Problems in Dermatology, 11, 6, (211), (1999). [doi.org]

  The non-specific erythematous scaly eruption is typically localised to moist and periorificial areas but may become generalised to resemble psoriasis, seborrhoeic dermatitis or ichthyosis. [dermnetnz.org]

  The classic clinical syndrome for vitamin B6 deficiency is a seborrheic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis (scaling on the lips and cracks at the corners of the mouth), conjunctivitis, intertrigo, sideroblastic [podiatrytoday.com]

• Suggestibility

  Further, proliferating cells accumulate biotin at a rate five times faster than quiescent cells; this observation suggests that there is an increased biotin requirement associated with cell proliferation. [ncbi.nlm.nih.gov]

  The research, published in the October issue of The American Journal of Clinical Nutrition, also suggests that smoking could lead to biotin deficiency and teratogenesis. [cabi.org]

• Renal Insufficiency

  Additional relevant MeSH terms: Layout table for MeSH terms Syndrome Kidney Failure, Chronic Psychomotor Agitation Restless Legs Syndrome Biotinidase Deficiency Disease Pathologic Processes Renal Insufficiency, Chronic Renal Insufficiency Kidney Diseases [clinicaltrials.gov]

• Kidney Failure

  Dialysis Renal Additional relevant MeSH terms: Layout table for MeSH terms Syndrome Kidney Failure, Chronic Psychomotor Agitation Restless Legs Syndrome Biotinidase Deficiency Disease Pathologic Processes Renal Insufficiency, Chronic Renal Insufficiency [clinicaltrials.gov]

• Seizure

  The seizures also diminished. This case shows that in young children with unexplained seizures that do not respond well to classic anticonvulsant therapy, the possibility of biotin deficiency should always be considered. [ncbi.nlm.nih.gov]

  Affected children may usually show symptoms like poor appetite, vomiting, tachypnea, hypotonia, irritability, lethargy, exfoliative dermatitis and seizures. The HCSD may progress into intractable seizures, cerebral edema and coma. [allnutriments.blogspot.com]

  Delayed treatment may result in neurological complications, including mental retardation, seizures and coma. [patient.info]

  The boy presented with perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. [en.wikipedia.org]

  These medications include antibiotics and anti-seizure drugs. Additionally, antibiotics destroy the good bacteria in your gut that can naturally produce biotin. 2. [healthline.com]

• Lethargy

  Urinary 3-hydroxy-isovalerate and slightly elevated levels of plasma branched-chain amino acids disappeared 1 week after oral supplementation with 1 mg day-1 of biotin as did the symptoms of orificial skin lesions, lethargy, hypotonia and alopecia later [ncbi.nlm.nih.gov]

  Neuropsychological diseases include depression, lethargy, hallucination, behavioral problems, seizures and numbness and tingling of the extremities. [allnutriments.blogspot.com]

  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. [symptoma.com]

  Urinary 3‐hydroxy‐isovalerate and slightly elevated levels of plasma branched‐chain amino acids disappeared 1 week after oral supplementation with 1 mg day ‐1 of biotin as did the symptoms of orificial skin lesions, lethargy, hypotonia and alopecia later [doi.org]

• Ataxia

  Other causes of ataxia. Other causes of sensorineural hearing loss. Investigations [ 1, 4 ] FBC, U&E, creatinine, LFTs, ± blood gases, urinalysis (for organic acids and ketones). Biotinidase (BTD), [ 8 ] carnitine, and acylcarnitine levels. [patient.info]

  Symptoms of biotin deficiency vary widely because biotin is involved in so many biochemical processes in the body. 4 Clinical signs may include: Anemia. 3 Ataxia. 7 Depression. 1, 5 Developmental delays. 18 Elevated cholesterol levels. 3 Fatigue. 1, 5 [biotin.com]

  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. [symptoma.com]

  […] all abstracts, three relevant studies were selected Relevant Paper(s) Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses Sutherland et al, 1991 274 Children with low IQ, seizures, hearing loss, ataxia [bestbets.org]

  BTD symptoms include, seizures, dermatitis, respiratory difficulties, hypotonia, hair loss, hearing loss, ataxia, reduced immune function and developmental delay. The symptoms can be kept under control by lifelong vitamin B7 supplementation. [allnutriments.blogspot.com]

• Paresthesia

  Hyperesthesia and Paresthesia Infants who are experiencing biotin deficiency may suffer from a condition called hyperesthesia, where the stimulation of the sense organ experiences an abnormal increase. [fitday.com]

  […] dermatitis Fungal infections Fine and brittle hair Hair loss or total alopecia Mild depression, which may progress to profound lassitude and, eventually, to somnolence Changes in mental status Generalized muscular pains (myalgias) Hyperesthesias and paresthesias [medicowesome.com]

  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. [symptoma.com]

  Paresthesia - In this condition a person who is suffering from a deficiency in biotin may experience tingling sensations similar to that of ‘falling asleep,’ in their hands, feet, arms and legs. [healthyhairplus.com]

  Here are signs that suggest biotin deficiency: Nerve pain: Numbness, tingling, prickly sensations, pain or any other "paresthesia." It can occur by itself, or as part of kidney disease, insulin resistance or diabetes. [gainesville.com]

• Somnolence

  […] biotin intake are: Dry skin Rashes, including erythematous periorofacial macular rash Seborrheic dermatitis Fungal infections Fine and brittle hair Hair loss or total alopecia Mild depression, which may progress to profound lassitude and, eventually, to somnolence [medicowesome.com]

  Deficiency Symptoms: Symptoms of biotin deficiency include erythematous exfoliative dermatitis, thinning hair, fatigue, irritability, mild depression, somnolence, muscle pains, anorexia, nausea, mild anemia. [info.spectracell.com]

  Fine and brittle hair Hair loss or total baldness (alopecia) Anemia Birth defects (still being studied) Seborrheic dermatitis Fungal infections Hallucinations Lethargy Anorexia Mild depression, which may progress to profound fatigue and, eventually, to somnolence [en.wikipedia.org]

  Rashes including erythematous periorofacial macular rash Fine and brittle hair Hair loss or total alopecia If left untreated, neurological symptoms can develop, including: Mild depression, which may progress to profound lassitude and, eventually, to somnolence [bodybuildingforyou.com]

  […] dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis (scaling on the lips and cracks at the corners of the mouth), conjunctivitis, intertrigo, sideroblastic anemia (due to impaired heme synthesis) and neurologic symptoms of somnolence [podiatrytoday.com]

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 [4]. The secondary effects of biotin deficiency can be measured through assessing the activities of biotin-dependent enzymes [4] [9]. Biotin is an essential cofactor for two acetyl-CoA carboxylases, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase [7]. 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 [4] [9].

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 [9]. 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 [10].

Other tests may include urine ketone and organic acid levels, and serum ammonia levels.

However, some of the treatments may require a doctor’s supervision, especially if the treatment is being administered to newborns. [durablehealth.net]

With treatment, patients may run a normal lifestyle and have an excellent prognosis [5]. Diagnosis is made by a blood test. Treatment is by oral biotin supplements. [nutrientsreview.com]

If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment. [babysfirsttest.org]

Pre-treatment EEG may show characteristic changes but may be normal after treatment. Management [ 1, 9 ] All patients with less than 10% biotinidase (BTD) activity should receive biotin supplements. [patient.info]

Diagnosis Signs, lesions, response to treatment/prevention. Differentiate from pantothenic acid deficiency (skin lesions). Treatment Addition of biotin in feed or water. [thepoultrysite.com]

The disorder has a good prognosis if biotin therapy is introduced early. If not, it can result in irreversible damage to the central nervous system and early death from metabolic acidosis. [ncbi.nlm.nih.gov]

With treatment, patients may run a normal lifestyle and have an excellent prognosis [5]. Diagnosis is made by a blood test. Treatment is by oral biotin supplements. [nutrientsreview.com]

The prognosis of the two above mentioned disorders (enzyme deficiencies) is usually good if biotin supplementation is started early and continued for life (45). Authored by Dr Peter Engel in 2010, reviewed and revised by Ines Warnke on 28.06.2017 [nutri-facts.org]

Prognosis [ 1 ] If the condition is treated promptly, no symptoms may arise. Delayed treatment may result in neurological complications, including mental retardation, seizures and coma. [patient.info]

There is evidence that impaired fatty acid metabolism secondary to reduced activities of the biotin-dependent carboxylases (especially acetyl-CoA carboxylase) plays an etiologic role in the dermatologic manifestations of biotin deficiency. [ncbi.nlm.nih.gov]

Biotin deficiency due to a defect in biotin transport has also been described. [25] Regardless of the etiology of biotin deficiency, clinical manifestations are similar. [emedicine.com]

[Values of tandem mass spectrometry in etiologic diagnosis of cerebral developmental retardation]. Zhonghua Er Ke Za Zhi 2007;45:932–6 Shevell M, Ashwal S, Donley D, et al. [bestbets.org]

Epidemiology Incidence is less than 1 in 60,000 babies - no more than 12 cases per year. [ 3 ] The carrier frequency in the general population is 1 in 120. [ 4 ] Presentation [ 1, 2 ] Usually presents aged 1 week to 2 years (earlier-onset carboxylase [patient.info]

A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4: 101-119. [omicsonline.org]

Textbook on Total Parenteral Nutrition in Children: Indications, Complications, and Pathophysiological Considerations : 89 – 108 Raven Press New York, NY. Mock 1990 ( 1990 ) Biotin. eds. [doi.org]

In summary, to prevent biotin deficiency, biotin should be added to the Japanese amino acid formula. [ncbi.nlm.nih.gov]

Medications Certain medicines may prevent your body from absorbing vitamins correctly. These medications include antibiotics and anti-seizure drugs. [healthline.com]

Prevention Supplementation of diets with biotin - naturally present in many raw materials, has very low bioavailability. [thepoultrysite.com]

[…] about its effectiveness in prevention or treatment of seborrheic dermatitis including Leiner’s disease in infants, acne, hair loss, brittle nails, diabetes or diabetic nerve pain [1,6]. [nutrientsreview.com]

The sad part is, thousands of medications are "drug muggers" of biotin, meaning they prevent absorption or diminish our ability to make it in the body. [gainesville.com]

1. Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology. 1997;49:1444–1447.
2. Sealey WM, Teague AM, Stratton SL, Mock DM. Smoking accelerates biotin catabolism in women. Am J Clin Nutr. 2004 Oct;80(4):932-935.
3. Perry CA, West AA, Gayle A, et al. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet. J Nutr. 2014 Dec;144(12):1977-1984.
4. Mock DM, Stadler DD, Stratton SL, Mock NI. Biotin status assessed longitudinally in pregnant women. J Nutr. 1997;127:710–716.
5. Mock DM. Marginal biotin deficiency is common in normal human pregnancy and is highly teratogenic in mice. J Nutr. 2009 Jan;139(1):154-157.
6. Tokuriki S, Hayashi H, Okuno T, et al. Biotin and carnitine profiles in preterm infants in Japan. Pediatr Int. 2013 Jun;55(3):342-345.
7. Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. 2008 November 1; 3(6):715–724.
8. Baykal T, Gokcay G, Gokdemir Y, et al. Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases. J Inherit Metab Dis. 2005;28(6):903-912.
9. Bogusiewicz A, Horvath TD, Stratton SL, Mock DM, Boysen G. Measurement of acylcarnitine substrate to product ratios specific to biotin-dependent carboxylases offers a combination of indicators of biotin status in humans. J Nutr. 2012;142(9):1621-1625.
10. Neto EC, Schulte J, Rubim R, et al. Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations. Braz J Med Biol Res. 2004 Mar. 37(3):295-299.