Biotin Deficiency Workup

  • Author: Noah S Scheinfeld, MD, JD, FAAD; Chief Editor: Jatinder Bhatia, MBBS   more...
 
Updated: Aug 1, 2011
 

Laboratory Studies

According to Neto et al, children with profound biotinidase deficiency have serum enzyme activity of less than 10% of mean normal activity.[4] Children with biotinidase deficiency commonly become symptomatic if caregivers do not administer biotin. Children who have partial biotinidase deficiency have 10-30% of mean normal serum biotinidase activity and can develop clinical manifestations of biotinidase deficiency when stressed by an infection or other systemic shocks.

Urine organic acid levels may be evaluated. Adults who consume raw egg whites for as few as 14-21 days excrete large amounts of β -hydroxyisovalerate in the urine.

Biotin levels may be assayed. In adults who consume raw egg whites for as few as 14-21 days, biotin levels in the urine and blood are considerably lower than healthy individuals.

The following tests are rarely needed because the diagnosis of biotin deficiency is primarily based on clinical findings. However, in cases with confusing findings, laboratory studies of the following may be useful:

  • Serum ammonia levels
  • Urine ketones levels
  • Quantitative plasma amino acid levels
  • Plasma carnitine levels, both free and total (sometimes termed free and esterified)
  • Routine serum chemistry panel

Moslinger et al assessed the effects of biotinidase deficiency and noted that a sensitive high-power liquid chromatography (HPLC) assay enabled discrimination of 5 patients with residual biotinidase activity (< 1%).[13] Two patients with 0 activities were homozygous for the G98:d7i3 mutation, and 3 patients (< 1%) with activities carried mutations G98:d7i3, R157H, and Q456H. The mutation spectrum of the remaining patients included T532M, A171T+D444H, V62M, C432W, and D444H.

In a Hungarian series of 58 patients, Laszlo et al noted 17 different mutations, consisting, in part, of 7 novel mutations.[5] Six of these new mutations were missense (245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A), and one was a unique allelic double mutation (212T>C; 236G>A).

Schulpis et al noted that the effects of neonatal jaundice on biotinidase activity are negative.[14] Low biotinidase activity can be expressed in full-term babies, premature babies, and small-for-date babies with jaundice. The low activity of the enzyme may be secondary to their impaired liver function. The high total bilirubin levels in the studied groups may inhibit the biotinidase enzyme. Gestational age, as well as total bilirubin levels, bear recording on Guthrie cards for correct evaluation of biotinidase activity.

Dobrowolski et al noted that, in the United States, the 4 mutations most commonly associated with complete biotinidase deficiency are c98:d7i3, Q456H, R538C, and the double mutation D444H:A171T.[15] Partial biotinidase deficiency is almost universally attributed to the D444H mutation.

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Imaging Studies

Spastic paraparesis was reported in patients with biotinidase deficiency, and symptoms began in later childhood and early adolescence. A 3-year-old male with biotinidase deficiency presented with skin eruption, ataxia, paraparesis, and MRI findings of myelopathy; all of which resolved with treatment.

Desai et al noted MRI findings in 4 patients and found (1) encephalopathy, low cerebral volume, ventriculomegaly, and widened extracerebral cerebrospinal fluid (CSF) spaces were common; (2) caudate involvement and parieto-occipital cortical abnormalities were uncommon; (3) a single patient had restricted diffusion; (4) 2 patients manifested with subdural effusions, and (5) 1H-magnetic resonance (MR) spectroscopy revealed decreased NAA peaks, elevated lactate levels, and reversal of the choline-to-creatine ratio.[16] With use of biotin, a total reversal of imaging findings occurred in 2 patients.

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Other Tests

Other tests are rarely indicated.

In cases with confusing findings, skin biopsy may be performed; however, the results are likely to be nonspecific and of little assistance.

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Procedures

No additional procedures are indicated.

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Histologic Findings

Little is known about possible histologic findings in biotin deficiency, probably because the diagnosis can be readily made based on careful history and physical examination findings. Therefore, histologic specimens are not needed.

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

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

Disclosure: Optigenex Consulting fee Independent contractor

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, and New York County Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

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  Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia

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

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Jatinder Bhatia, MBBS  Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia

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

Disclosure: Nothing to disclose.

Acknowledgments

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

References

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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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