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Biotin Deficiency Clinical Presentation

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
 
Updated: Jan 31, 2016
 

History

Profound biotinidase deficiency can be detected with newborn screening. The first symptoms of biotin deficiency are associated with the skin and hair.

Symptoms develop within 3-5 weeks of the onset of deficient biotin intake. The most common cutaneous findings include the following:

  • Dry skin
  • Seborrheic dermatitis
  • Fungal infections
  • Rashes, including erythematous periorofacial macular rash
  • Fine and brittle hair
  • Hair loss or total alopecia

Approximately 1-2 weeks later, neurologic symptoms begin to develop. The most common neurologic findings include the following:

  • Mild depression, which may progress to profound lassitude and, eventually, to somnolence
  • Changes in mental status
  • Generalized muscular pains (myalgias)
  • Hyperesthesias and paresthesias

Intestinal tract symptoms also develop and most commonly include the following:

  • Nausea, occasionally severe
  • Vomiting
  • Anorexia

Spastic tetraparesis in a young woman associated with deficiency of biotinidase has been reported.[17]

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Physical

Individuals with biotin deficiency are typically healthy before the onset of the biotin-deficient state. Growth and stature are normal. Regardless of the etiology of biotin deficiency, clinical manifestations are essentially the same in all patients; however, the rate of symptom development and the sequence in which symptoms appear greatly vary. Physical manifestations are confined to the skin and hair, central and peripheral nervous systems, and intestinal tract.

Skin and hair

The first signs that develop in biotin deficiency are associated with the skin and hair. Dry skin is a consistent finding and is often associated with seborrheic dermatitis, which can be severe. The skin lesions provide an ideal environment for fungal infections that may be resistant to treatment until the biotin-deficient state is reversed. An erythematous periorofacial macular rash is a common finding. The hair quickly becomes fine and brittle, and total alopecia often develops.

Hearing

Genc et al performed subjective and objective audiologic tests on 20 children with profound biotinidase deficiency and found that approximately 55% of children with biotinidase deficiency develop sensorineural hearing loss.[18] The hearing loss varies in severity from mild to profound.

Central and peripheral nervous systems

The neurologic signs are multiple and nonspecific. They include mild depression, which may progress to profound lassitude, and, eventually, somnolence. Occasionally, changes in mental status are observed. Generalized muscular pains (myalgias), hyperesthesias, and paresthesias are common findings that occasionally become disabling. Profound biotinidase deficiency in a 3-year-old boy with progressive spastic paraparesis and ascending weakness but not the typical neurological symptoms was noted by Chedrawi et al.[19] Biotinidase deficiency with hypertonia was noted by Rathi and Rathi.[20] Biotin-responsive seizures and encephalopathy due to biotinidase deficiency have been noted.[21]

Intestinal tract

Nausea, occasionally severe, is an occasional finding, as is anorexia. These problems are rarely severe enough to significantly interfere with the adequate oral intake of food.

Biotin responsive seizures and encephalopathy due to biotinidase deficiency has been reported.

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Causes

Causes of biotin deficiency include the following:

Eating raw egg whites

Some mistakenly believe that raw egg-white consumption is the only cause of biotin deficiency. Nonetheless, a diet that contains raw egg whites quickly and almost invariably leads to biotin deficiency.

Total parenteral nutrition without biotin supplementation

Several cases of biotin deficiency in patients receiving prolonged total parenteral nutrition (TPN) therapy without added biotin have been reported. Therefore, all patients receiving TPN must also receive biotin at the recommended daily dose, especially if TPN therapy is expected to last more than 1 week. All hospital pharmacies currently include biotin in TPN preparations.

Anticonvulsant therapy

Prolonged use of certain drugs, especially phenytoin, primidone, and carbamazepine, may lead to biotin deficiency; however, valproic acid therapy does not cause this condition. Some anticonvulsants inhibit biotin transport across the intestinal mucosa. Evidence suggests that these anticonvulsants accelerate biotin catabolism. Therefore, supplemental biotin, in addition to the usual minimum daily requirements, has been suggested for patients who are treated with anticonvulsants that have been linked to biotin deficiency.

Prolonged oral antibiotic therapy

Prolonged use of oral antibiotics has been associated with biotin deficiency. Alterations in the intestinal flora caused by the prolonged administration of antibiotics are presumed to be the basis for biotin deficiency.

Genetic mutation

Mikati et al reported a case of partial biotinidase deficiency (plasma biotinidase level of 1.3 nm/min/mL) in a 7-month-old boy.[22] The boy presented with perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. The child's neurologic symptoms abated following biotin supplementation and antiepileptic drug therapy. DNA mutational analysis revealed that the child was homozygous for a novel E64K mutation and that his mother and father were heterozygous for the novel E64K mutation. We now report 140 known mutations in the biotinidase gene (BTD) that cause biotinidase deficiency.

Ketogenic diet (high-protein, low-fat)

In a mouse model, a ketogenic diet exaggerated biotin deficiency.[7]

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

Coauthor(s)

Stephanie Beth Freilich, MD Clinical Instructor, Department of Pediatrics, Mount Sinai School of Medicine; Clinical Assistant, Department of Pediatrics, Mount Sinai Hospital

Stephanie Beth Freilich, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, New York County Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jatinder Bhatia, MBBS, FAAP Professor of Pediatrics, Medical College of Georgia, Georgia Regents University; Chief, Division of Neonatology, Director, Fellowship Program in Neonatal-Perinatal Medicine, Director, Transport/ECMO/Nutrition, Vice Chair, Clinical Research, Department of Pediatrics, Children's Hospital of Georgia

Jatinder Bhatia, MBBS, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Society for Nutrition, American Society for Parenteral and Enteral Nutrition, Academy of Nutrition and Dietetics, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Gerber.

Chief Editor

Jatinder Bhatia, MBBS, FAAP Professor of Pediatrics, Medical College of Georgia, Georgia Regents University; Chief, Division of Neonatology, Director, Fellowship Program in Neonatal-Perinatal Medicine, Director, Transport/ECMO/Nutrition, Vice Chair, Clinical Research, Department of Pediatrics, Children's Hospital of Georgia

Jatinder Bhatia, MBBS, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Society for Nutrition, American Society for Parenteral and Enteral Nutrition, Academy of Nutrition and Dietetics, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Gerber.

Additional Contributors

Maria Rebello Mascarenhas, MBBS Associate Professor of Pediatrics, University of Pennsylvania School of Medicine; Section Chief of Nutrition, Division of Gastroenterology and Nutrition, Director, Nutrition Support Service, Children's Hospital of Philadelphia

Maria Rebello Mascarenhas, MBBS is a member of the following medical societies: American Gastroenterological Association, American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Howard R Sloan, MD, PhD†, to the development and writing of this article.

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Biotin is a bicyclic (more precisely, heterocyclic) compound composed of an ureido ring (A) fused with a tetrahydrothiophene ring (B). A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring.
Carboxybiotin carboxylase is the activated form of a carboxylase that conducts the actual carboxylation of a substrate. The CO2 residue attached to the nitrogen atom diagonally across from the valeric acid substituent is transferred to the substrate to be carboxylated, and the original carboxylase is liberated intact.
Depiction of the flow of biotin in the biotin cycle.
Biocytin is the product of the complete proteolysis of biotin-containing proteins and peptides. The enzyme biotinidase cleaves biocytin into free biotin and the amino acid lysine. The free biotin is then available for intestinal absorption or intracellular coupling to an apocarboxylase to form a holocarboxylase.
The biotin molecule is bound to the protein by a peptide bond to an e-amino group of an apocarboxylase to form a holocarboxylase.
 
 
 
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