Biotinidase deficiency is an inherited metabolic disorder that prevents the body from recycling the vitamin biotin, which is necessary for metabolizing fats, proteins, and carbohydrates. Without the ability to reuse biotin, individuals can develop serious health issues. Newborn screening is a public health program that tests infants for treatable conditions shortly after birth. Including biotinidase deficiency in these screenings allows for early identification and intervention, preventing the disorder’s harmful effects.
The Newborn Screening Process
The process for detecting biotinidase deficiency begins within a baby’s first few days of life. A heel prick is used to collect a few drops of blood, which are blotted onto special filter paper to create a dried blood spot. This method is efficient for collecting and transporting the sample to a lab for analysis.
The dried blood spot card is sent to a state or regional laboratory for analysis. Technicians perform a test on the blood sample to measure the activity level of the biotinidase enzyme. Low or absent enzyme activity suggests a potential biotinidase deficiency and requires follow-up with the infant’s healthcare provider.
Understanding Screening Results
A healthcare provider will contact the parents if a screening result is “out-of-range” or “presumptive positive.” This initial finding is not a definitive diagnosis, as factors like prematurity or sample exposure to heat can cause a false positive. A repeat test is often necessary to confirm the results.
An out-of-range result means the biotinidase enzyme activity was lower than normal. The screening differentiates between two main types based on the level of activity. Profound biotinidase deficiency is diagnosed when there is less than 10% of normal enzyme activity, while partial biotinidase deficiency involves 10-30% of normal activity.
Each classification points to a different level of severity if left untreated. Profound deficiency carries a higher risk of developing health problems. Partial deficiency may lead to milder symptoms, often only during times of illness or stress, and this initial classification helps guide the follow-up testing.
Confirmatory Diagnosis and Genetic Basis
After a presumptive positive screening, confirmatory testing is the next step. This involves collecting a serum or plasma sample from a vein for a quantitative enzyme assay. This test provides a precise measurement of the biotinidase enzyme’s activity level.
Biotinidase deficiency is an autosomal recessive disorder, meaning an infant inherits two non-working copies of a gene, one from each parent. The gene responsible for the biotinidase enzyme is the BTD gene. Mutations in both copies of the BTD gene result in an enzyme with little to no function. Parents of an affected child are carriers, having one working and one non-working copy of the gene, and do not show symptoms.
Genetic testing can be performed to finalize the diagnosis by identifying the specific disease-causing mutations in the BTD gene. For example, a common mutation known as p.D444H is frequently responsible for partial biotinidase deficiency. Confirming the diagnosis with both enzyme and genetic tests provides a complete picture of the condition.
Treatment and Long-Term Outlook
Once a diagnosis is confirmed, treatment for biotinidase deficiency is highly effective. It consists of a daily oral supplement of biotin, a form of vitamin B7. This therapy provides the free biotin the body cannot recycle, allowing enzymes to function correctly, and must be continued for life.
When started early and taken consistently, biotin therapy prevents associated health problems like seizures, hair loss, skin rashes, and developmental delays. Individuals with either profound or partial biotinidase deficiency who are identified through newborn screening and adhere to treatment can expect to lead full and healthy lives.