NORD gratefully acknowledges Matthew Walsh, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Biotinidase deficiency (BTD) deficiency is a treatable, inherited condition. BTD affects the way the body processes a vitamin called biotin (sometimes called vitamin H). Biotin is an important vitamin that helps the body break down protein, fats, and carbohydrates.
Biotinidase is an enzyme that helps recycle biotin to be reused by the body. Bitotinidase deficiency happens when this enzyme this isn’t working properly. BTD is caused by genetic changes (mutations) in the BTD gene.
If untreated, BTD can cause health problems such as:
BTD can have other features as well, including skin differences like rashes (eczema) and hair loss (alopecia).
BTD can be treated by giving people with the condition extra biotin for their body to use. If treated early, people with BTD can avoid all symptoms of the condition and lead a normal, healthy life.
Biotinidase deficiency is sometimes categorized into groups depending on how much of the biotinidase enzyme is working. These two categories are profound BTD and partial BTD. People with profound BTD tend to have more severe symptoms earlier in life than people with partial BTD. Both forms of BTD can be treated with biotin supplements. Early diagnosis and treatment of BTD can prevent symptoms from happening. Nearly all infants with either profound or partial BTD can be detected in the US by newborn screening. However, not every country has added BTD to its newborn screening program.
Infants with BTD may be born without signs of the condition. Symptoms of BTD usually appear after the first few weeks or months of life. Treating BTD with biotin supplements before symptoms show up can prevent them from happening. Below is a list of symptoms that infants and children with profound untreated BTD may have. It is important to know that not every person with BTD will show all of these symptoms.
Many of the symptoms of BTD are neurological, which means they affect the brain and nervous system.
About 70% of infants with BTD will experience seizures if they are not treated. This is often the first symptom of the condition. Seizures in infants may look different than seizures in adults. Some signs of seizures in infants include:
Because the seizures are caused by the body being unable to recycle biotin, they may not stop with seizure medications (anticonvulsants). However, the seizures do respond to biotin therapy and often should stop within minutes to hours of receiving biotin treatment.
Some infants with BTD may have weak muscles and low muscle tone. This is called hypotonia. Infants with hypotonia may look abnormally “floppy.” Hypotonia can affect feeding and motor skills such sitting up without assistance.
Affected infants and children may experience delays in reaching developmental milestones, including holding one’s head up or pulling up to stand.
Infants with BTD may also have problems with vision or hearing. These issues can be prevented if biotin therapy is started early.
Some other common features of BTD include eye infections, like pink eye (conjunctivitis), hair loss (alopecia), and a certain type of skin rash called eczema.
Infants with BTD may have specific molecules in their urine, such as lactic acid (lactic aciduria) or low but noticeable amounts of ammonia.
Some infants may have other symptoms like:
Without treatment with biotin, infants with BTD can develop coma and may even die.
Children and adults with partial biotinidase who don’t receive biotin supplements may show mild symptoms of the condition during times of stress, like times of illness.
Biotinidase deficiency is a genetic disorder caused by changes (mutations) in the BTD gene. The BTD gene instructs the body in creating the enzyme biotinidase that helps the body recycle an important vitamin called biotin (vitamin H). When the body is not able to recycle biotin, health concerns like the symptoms above can happen.
We all have two copies of every gene. We inherit one copy from out mother and one copy from our father. Genetic diseases are determined by the combination of genes received from our father and mother. Biotinidase deficiency is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits the same non-working 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 non-working 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 20-30 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.
Biotinidase deficiency is a rare disorder. The early-onset form (profound BTD) usually begins during the newborn (neonatal) period. The juvenile form (partial BTD) usually begins at about three months of age. Both males and females are affected in equal numbers.
One in 140,000 people have profound biotinidase deficiency.
One in 110,000 people have partial biotinidase deficiency.
One in 60,000 people have either profound or partial biotinidase deficiency.
Approximately 1 in 120 people are carriers of one gene for BTD, but this number may be higher in the Hispanic population and lower in the African American population.
Biotinidase deficiency can be diagnosed in newborns through newborn screening. Newborn screening is a special type of screening test that newborns receive to see if they have certain diseases. Because the newborn screen is a screening test, a positive result does not mean that an infant definitely has the disease. Often, a repeat test must be done to confirm the diagnosis. A clinical diagnosis is possible after birth by testing for biotinidase activity in the blood. Usually, this is performed when signs and symptoms of BTD become clearer. In some infants, a genetic test may be ordered to identify the specific gene changes (mutation) that are causing BTD. Prenatal testing of sample fluid from the womb for biotinidase activity is available as early as 12 weeks of pregnancy (this includes chorionic villi sampling and amniocentesis).
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 person with biotinidase deficiency may have to take biotin for his/her entire lifetime.
Genetic counseling is recommended for families of a child with biotinidase deficiency. Genetic counselors are healthcare providers that help families understand genetic conditions and make genetic testing decisions.
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Porta F, Pagliardini V, Celestino I, et al. Neonatal screening for biotinidase deficiency: A
30-year single center experience. Mol Genet Metab Rep. 2017;13:80-82.
Wolf B. Successful outcomes of older adolescents and adults with profound biotinidase
deficiency identified by newborn screening. Genet Med. 2017;19(4):396-402.
Jay AM, Conway RL, Feldman GL, Nahhas F, Spencer L, Wolf B. Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years. Genet Med. 2015;17(3):205-209.
Cowan TM, Kazerouni NN, Dharajiya N, Lorey F, Roberson M, Hodgkinson C, Schrijver I. Increased incidence of profound biotinidase deficiency among Hispanic newborns in California. Mol Genet Metab. 2012;106:485–7.
Wolf B. The neurology of biotinidase deficiency. Mol Genet Metab. 2011;104(1-2):27-34.
Wolf B. Clinical issues and frequent questions about biotinidase deficiency. Mol Genet
Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. 2008;3(6):715-724.
Wolf B, Pomponio RJ, Norrgard KJ, et al. Delayed-onset profound biotinidase
deficiency. J Pediatr. 1998;132(2):362-365.
Orphanet. Biotinidase deficiency. Last Edit Date: July 2011. Orphanet [Internet]. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79241 Accessed April 10, 2019.
McKusick VA, Ed. Online Mendelian Inheritance in Man(OMIM). The Johns Hopkins University. Biotinidase Deficiency. Entry Number 253260. Last Edit Date: 9/9/2016. Available at: http://omim.org/entry/253260 Accessed April 10, 2019.
Wolf B. Biotinidase Deficiency. 2000 Mar 24 [Updated 2016 Jun 9]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1322/ Accessed April 10, 2019.
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