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.
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.
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.
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