Biotinidase Deficiency Screening -Infant

Biotinidase Deficiency Screening -Infant

Biotinidase Deficiency Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The genetic screening for Biotinidase Deficiency is recommended.

B

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.

OVERVIEW

An inherited disorder in which the body is unable to reuse and recycle biotin, a B vitamin found in foods such as liver, egg yolks and milk. The BTD gene is responsible for making biotinidase which, in turn, is responsible for extraction of biotin from ingested dietary sources and recycling of biotin from endogenous sources (breakdown of endogenous proteins). Biotin is an essential cofactor for several carboxylase enzymes that are required to process proteins, fats, or carbohydrates. The developing brain is particularly sensitive to biotin deficiency. Patients usually appear perfectly normal at birth, but can develop irreversible hearing and vision loss if untreated.

SCREENING

Finding

Decreased activity of biotinidase, an enzyme that releases biotin (vitamin H) from proteins

Tested By

Colorimetric, semiquantitative enzyme assay; false positives may occur in premature infants and in samples placed in plastic before sufficient drying or exposed to excessive heat.

PREVALENCE

Prevalence is 1:60,000 overall; 1 :130,000 for profound deficiency and 1:110,00 for partial deficiency; carrier (heterozygous for BTD mutation) frequency is about 1:120

INHERITANCE

BTD is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified.

OTHER TESTING

Genetic testing is possible for at-risk family members. Carriers can be diagnosed with 95% accuracy by enzyme assay, but DNA testing is superior for this purpose being less affected by temperature or sample handling.

CLINICAL CHARACTERISTICS

With treatment, clinical outcomes are excellent. Without treatment, outcomes depend on the inherent severity of disease in the affected patient. In the severe form, with profound biotinidase deficiency (enzyme activity <10% of normal), neurologic injury, hearing loss, blindness, and death may result. Symptoms may develop as soon as the first week of life or as late as 10 years of age (mean age of 3 1/2 months).

Initial symptoms/signs may include:

  • seizures
  • hypotonia
  • hyperventilation, laryngeal stridor, and/or apnea
  • eczematoid rash
  • alopecia
  • conjunctivitis
  • candidiasis
  • ataxia

 

Older children may manifest:

  • limb weakness
  • paresis
  • developmental delay
  • neurosensory hearing loss
  • optic atrophy and scotomata
  • recurrent viral and fungal infections

 

Children with untreated partial biotinidase deficiency may manifest any of the above symptoms, though generally they will be mild and occur only with concomitant stressors, such as prolonged infection.

EARLY SIGNS

There are two main types of biotinidase deficiency (BIOT), differing in the severity of signs: severe “profound biotinidase deficiency” and mild “partial biotinidase deficiency.” 

Signs of BIOT usually start within a few months after birth. In some cases, the symptoms may not appear until childhood. This is why early screening and identification is so important.

Early signs of BIOT include:

  • Seizures 
  • Weak muscle tone (known as hypotonia)
  • Trouble breathing
  • Skin rash
  • Hair loss
  • Trouble balancing
  • A fungal infection called candidiasis

Many of these signs can be triggered by illnesses or infections.

CAUSES

When we eat food, enzymes help break it down.  One of these enzymes, biotinidase, helps us reuse and recycle the vitamin biotin.  Our bodies need biotin to help break down fats, proteins and carbohydrates. 

If your baby has biotinidase deficiency (BIOT), then his or her body either does not make enough or makes non-working biotinidase enzyme. When biotinidase is not working correctly, biotin cannot be recycled and reused. If biotin cannot be recycled, then there will not be enough biotin to break down carbohydrates, fats, and proteins. Carbohydrates, fats, and proteins then build-up in the blood, which can be harmful.

BIOT is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for BIOT, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with BIOT is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Supplements

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. to measure the levels of certain substances in the child’s blood. 

EXPECTED OUTCOMES

If biotinidase deficiency (BIOT) is treated, your child will likely have healthy growth and development.

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.