Biotinidase Deficiency (BTD)


Biotinidase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. If this condition is not recognized and treated, its signs and symptoms typically appear within the first few months of life, although it can also become apparent later in childhood. This is why Newborn Screening is necessary.

Other names –

  • BIOT
  • carboxylase deficiency, multiple, late-onset
  • late-onset biotin-responsive multiple carboxylase deficiency
  • late-onset multiple carboxylase deficiency
  • multiple carboxylase deficiency, late-onset

Incidence –

The incidence of profound biotinidase deficiency is approximately 1 in 137,000 births. The prevalence of partial biotinidase deficiency is approximately 1 in 110,000 people. Since partial biotinidase deficiency can be mild, it is possible that the true prevalence is more common.

The condition is most common among individuals of European descent. However, it is also reported among individuals of Turkish, Saudi Arabian, and Japanese descent.

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.


This condition is inherited in an autosomal recessive pattern. The parents of an individual with biotinidase deficiency each carry one copy of the mutated gene, but they typically do not have any health problems associated with the condition.

Cause –

Mutations in the BTD gene cause biotinidase deficiency. The BTD gene provides instructions for making an enzyme called biotinidase. This enzyme recycles biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Biotinidase removes biotin that is bound to proteins in food, leaving the vitamin in its free (unbound) state. Free biotin is needed by enzymes called biotin-dependent carboxylases to break down fats, proteins, and carbohydrates. Because several of these enzymes are impaired in biotinidase deficiency, the condition is considered a form of multiple carboxylase deficiency.

Effect on Regulations

Mutations in the BTD gene reduce or eliminate the activity of biotinidase. Profound biotinidase deficiency results when the activity of biotinidase is reduced to less than 10 percent of normal. Partial biotinidase deficiency occurs when biotinidase activity is reduced to between 10 percent and 30 percent of normal. Without enough of this enzyme, biotin cannot be recycled. The resulting shortage of free biotin impairs the activity of biotin-dependent carboxylases, leading to a buildup of potentially toxic compounds in the body. If the condition is not treated promptly, this buildup damages various cells and tissues, causing the signs and symptoms described above.


  • 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.


There are two types. Individuals who have less than 10% of the normal amount of the enzyme biotinidase are said to have profound biotinidase deficiency. Individuals who have between 10% and 30% of the normal amounts of biotinidase have a milder form of the disease known as partial biotinidase deficiency.

Profound biotinidase deficiency is the more severe form of the condition.

Symptoms –

It can cause –

  • seizures,
  • weak muscle tone (hypotonia),
  • breathing problems,
  • hearing and vision loss,
  • problems with movement and balance (ataxia),
  • skin rashes, hair loss (alopecia), and
  • a fungal infection called candidiasis.
  • Affected children also have delayed development.

Partial biotinidase deficiency is a milder form of this condition.

Symptoms –

Without treatment, affected children may experience

  • hypotonia,
  • skin rashes, and
  • hair loss,

but these problems may appear only during illness, infection, or other times of stress.

Outcome –

Lifelong treatment can prevent these complications from occurring or improve them if they have already developed.

It is important to screen for and treat BIOT early because once your child experiences certain medical complications such as developmental delay, eye abnormalities, or hearing loss, treatment cannot reverse any damage that has occurred.

Screening and Diagnosis –

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 diagnosis may be obtained through the examination of a family history. Prenatal testing of sample fluid from the womb for biotinidase activity is available.

Treatment –

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. Genetic counseling is recommended for families of a child with multiple carboxylase deficiency.

Children with biotinidase deficiency (BIOT) often require lifelong treatment with biotin supplements. This is a natural vitamin found in food, but children with BIOT might not have enough of it in their bodies. Biotin supplements can help your baby’s body break down the fats, proteins, and carbohydrates found in food. Your baby’s doctor can help determine the right dosage of biotin for your child and write an appropriate prescription.

References –

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