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Biotinidase deficiency

Synonyms of Biotinidase deficiency

  • BTD deficiency
  • Infantile multiple carboxylase deficiency
  • Juvenile multiple carboxylase deficiency
  • Late-onset multiple carboxylase deficiency
  • Multiple carboxylase deficiency, due to biotinidase deficiency

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Biotinidase deficiency (BTD) is a treatable, metabolic disorder that is the result of a low concentration, or complete lack, of the enzyme, biotinidase. Biotinidase deficiency is an inherited disorder in which the body is not able to properly process the vitamin, biotin, which is sometimes referred to as Vitamin H. Biotin is an essential vitamin to the metabolic process and biotinidase, among its other functions, allows biotin to become available for use by the body. Mutations in the BTD gene cause biotinidase deficiency. The genetic traits associated with biotinidase deficiency are transmitted in an autosomal recessive manner.

Most infants with BTD show signs of lactic acid in the urine (aciduria), a widespread, red, skin rash (eczema), seizures, poor muscle tone (hypotonia), developmental delays, and hair loss (alopecia). Daily treatment with biotin supplements will clear up these symptoms.


Babies may be born without signs of biotinidase deficiency, but the symptoms become apparent after the first few weeks or months of life. Chief characteristics include weak muscles (hypotonia), seizures, hair loss (alopecia), an inflammatory skin rash (eczema), developmental delays, and lactic aciduria.

Between 25 to 50 percent of infants born with BTD exhibit one or more of these characteristics: poor coordination (ataxia), red-eye (conjunctivitis), hearing loss, drowsiness (lethargy), low but appreciable concentrations of ammonia in blood serum, breathing problems and sight problems.

Between 10 to 25 percent of infants born with BTD exhibit one or more of these characteristics: periods of unconsciousness (coma), vomiting, diarrhea, and fungus infections.

Fewer than 10 percent of infants born with BTD exhibit one or more of these characteristics: enlarged liver (hepatomegaly), enlarged spleen (splenomegaly), and speech problems.


Biotinidase deficiency is an autosomal recessive hereditary disorder caused by a fault (mutation) in the gene known as the BTD gene, The BTD gene allows for the body's production of the enzyme (protein) that separates the essential vitamin, biotin, making it available for the body's metabolism.

The BTD gene has been traced to the long arm of chromosome 3 at gene map locus 3p25. Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 3p25" refers to band 25 on the short (p) arm of chromosome 3.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Biotinidase deficiency is a rare disorder. The early-onset form usually begins during the newborn (neonatal) period. The juvenile form usually begins at about three months of age. Males and females are affected in equal numbers.

Related Disorders

Holocarboxylase synthetase deficiency (HCSD)
Physicians may have difficulty distinguishing between biotinidase deficiency and holocarboxylase synthetase deficiency. Many of the symptoms are similar and each is responsive to treatment with biotin. Both conditions are acquired through autosomal recessive genetics. The term holocarboxylase refers to an enzymatic, chemical process in which any of three complex organic acids may be involved. These three complex organic acids are normal body metabolites that require biotin as a co-factor. Because the chemical process involved is the same for each of the three organic acids, the disorder was termed "multiple carboxylase deficiency".

Isolated carboxylase deficiency
As noted above, biotin is required to build up or break down (metabolize) any of three complex organic acids. If a mutation occurs, in the appropriate gene, such that the reaction involving one of these organic acids fails, then the resulting disorder is known as an "isolated carboxylase deficienc". Many of the symptoms and signs of these isolated carboxylase reactions are similar to those exhibited by patients with BTD and HCSD.

Standard Therapies

A diagnosis of biotinidase deficiency is performed in newborns through screening. A clinical diagnosis is possible after birth by testing for blood serum biotinidase activity, This is performed when signs and symptoms of BTD become clearer. In addition, a positive diagnoses may be obtained through the examination of a family history. Prenatal testing of sample fluid from the womb for biotinidase activity is available.

Biotinidase deficiency is treated with oral biotin (vitamin H; coenzyme R, part of vitamin B complex) supplements. Treatment should begin as soon as the diagnosis is made. With biotin treatment, symptoms of the disorder may disappear. However, a patient may have to take Biotin for an entire lifetime. Genetic counseling is recommended for families of a child with multiple carboxylase deficiency.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources contact:

Biotinidase deficiency Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at

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Nyhan WM. Multiple Carboxylase Deficiency. (Biotinidase Deficiency). In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:482.

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:49.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:652-660.

Wolf B. Disorders of Biotin Metabolism. In: Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:3935-56.

Gonzalez EC, Marrero N, Frometa A, Herrera D, Castells E, Perez PL. Qualitative colorimetric ultramicroassay for the detection of biotinidase deficiency in newborns. Clin Chem Acta. 2006;369:35-39.

Hendriksz CJ, preece MA, Chakrapani A. Successful pregnancy in treated patient with biotinidase deficiency. J Inherit Metab Dis. 2005;28:791-92.

Wolf B, Jensen K. Evolutionary conservation of biotinidase: implications for the enzyme's structure and subcellular localization. Mol Genet Metab. 2005;86:44-50.

Wolf B. Biotinidase: its role in biotinidase deficiency and biotin metabolism. J Nutr Biochem. 2005;16:441-45.

Hoffman TL, Simon EM, Ficicioglu C. Biotinidase deficiency: the importance of adequate follow-up for an inconclusive newborn screening result. Eur J Pediatr. 2005;164:298-301.

Wolf B, Freehauf CL, Thomas JA, Gordon PL, Greene CL, Ward JC. Markedly elevated serum biotinidase activity may indicate glycogen storage disease type Ia. J Inherit Metab Dis. 2003;26:805-09.

McKusick VA, Ed. Online Mendelian Inheritance in Man(OMIM). The Johns Hopkins University. Biotinidase Deficiency. Entry Number; 253260: Last Edit Date: 4/6/2005.

Wolf B. Biotinidase Deficiency. GENEReviews. Last Update: 2 March 2006. 24pp. Accessed 11/7/2006

Thibodeau DL, Wolf B. Biotinidase Deficiency: a Booklet for Families & Professionals. Last Updated: 02.01.02. 19pp. Accessed 11/7/2006

DiFazio MP. Biotinidase Deficiency. emedicine. Last Updated: March 26, 2006. 11pp. Accessed 11/7/2006

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2007/09/23 00:00:00 GMT+0

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