Biotinidase deficiency, a metabolic disorder, is a genetically transmitted condition and is reportedly common in our country. Since 2007, screening newborns for this deficiency through heel prick tests has been a crucial step toward early diagnosis and treatment. Biotinidase deficiency (BIOT) is a hereditary condition in which the body cannot properly utilize and recycle the vitamin biotin. This means the body cannot access the biotin necessary to effectively break down fats, proteins, and carbohydrates.

BIOT encompasses two types, varying in severity and treatment. Both forms can lead to serious health problems. Children with BIOT diagnosed early through newborn screening generally develop normally when promptly treated. Therefore, early diagnosis and treatment are crucial.

Turkey stands out as one of the countries with a high prevalence of biotinidase deficiency worldwide. Therefore, the inclusion of biotinidase deficiency in newborn screening programs in Türkiye is an important step taken by health authorities to control this genetic condition.

Biotinidase deficiency symptoms: Early and severity differences

Symptoms of biotinidase deficiency (BIOT) vary in severity between the two main types, “severe profound biotinidase deficiency” and “mild partial biotinidase deficiency.”

Symptoms of BIOT usually begin a few months after birth, but in some cases, they can appear as early as childhood. Therefore, early screening and diagnosis are important.

Some early symptoms include:

• Seizures
• poor muscle tone
• Difficulty breathing
• skin rash
• Hair loss
• Balance problems
• Candidiasis (fungal infection)

Because these symptoms can often be triggered by other illnesses or infections, if you notice any of these symptoms in your baby, you should consult your healthcare provider as soon as possible. Early diagnosis plays a key role in managing and treating biotinidase deficiency.

Causes of biotinidase deficiency

When we eat, enzymes in the body play a crucial role in breaking down and decomposing nutrients. The enzyme biotinidase, involved in this process, helps the body recycle the vitamin biotin and utilize it. Our bodies need biotin to effectively break down fats, proteins, and carbohydrates.

In cases of biotinidase deficiency (BIOT), the body either cannot produce enough biotin or the biotinidase enzyme needed to recycle biotin is not functioning properly. In this case, biotin cannot be recycled or reused. Insufficient biotin utilization results in the inability to effectively break down carbohydrates, fats, and proteins. These nutrients accumulate in the blood and can be harmful.

Biotinidase deficiency is an autosomal recessive genetic condition, meaning a child must inherit the condition from both parents. Parents can often be carriers of the condition, but they often do not show signs or symptoms. When parents who carry the condition come together, their children may develop biotinidase deficiency. While this condition is rare, there is a risk of having more than one child if both parents are carriers.

How is biotinidase deficiency (biot) diagnosed?

Diagnosis of biotinidase deficiency is often made as part of newborn screening programs. Newborn screening is an important step toward early detection of genetic conditions such as biotinidase deficiency. During these screenings, the child's biotinidase levels are checked at regular intervals.

If newborn screening results fall outside established reference ranges, the pediatrician may request additional testing. These additional tests are typically performed to confirm biotinidase deficiency and assess its severity. The doctor may perform further testing, particularly if certain symptoms or risk factors are present.

Diagnosing biotinidase deficiency typically involves blood tests and genetic analysis. These tests measure biotinidase enzyme levels and identify genetic mutations. Early diagnosis is crucial for developing a rapid treatment plan, as early treatment can help children with biotinidase deficiency grow up healthy.

Treatment of biotinidase deficiency (BIOT):

Children with biotinidase deficiency are typically treated with lifelong biotin supplements. Biotin is a vitamin found naturally in foods, but children with biotinidase deficiency may not produce enough of it. Therefore, biotin supplements are used to correct the deficiency.

Treatment usually includes the following steps:

• Biotin supplements: A pediatrician determines the appropriate biotin dose based on the needs of a child with BIOT. This dose is adjusted based on the child's age, weight, and severity of the disease. Biotin supplements help the child's body effectively break down fats, proteins, and carbohydrates.
• Regular checkups: Regular checkups with your doctor are important during treatment. Your doctor can monitor your child's biotin levels to adjust the dosage and assess their overall health.
• Special diet: In some cases, children with biotinidase deficiency may be placed on a special diet. A doctor can create an appropriate diet plan based on the child's needs.

When provided regular treatment with biotin supplements, children with BIOT can generally grow up healthy and lead normal lives.

Consequences of untreated biotinidase deficiency

If biotinidase deficiency is left untreated, young children and infants with profound biotinidase deficiency can develop serious neurological abnormalities and other health problems. This can manifest as:

• Seizures: Untreated biotinidase deficiency can cause seizures in children. Infants with profound biotinidase deficiency often exhibit this symptom.
• Motor limb weakness: In older children and adolescents, the condition can lead to motor limb weakness if left untreated. Spastic paresis, or muscle rigidity and loss of control, is associated with this condition.
• Developmental delay: Untreated biotinidase deficiency can negatively impact normal development in children. A developmental delay means that a child is behind in acquiring age-appropriate skills.
• Vision and hearing problems: Profound biotinidase deficiency can cause vision problems, hearing loss, and other neurological abnormalities. These problems can often be irreversible, especially if left untreated.
• Dermatological problems: Skin rashes, hair loss and other dermatological problems may be associated with biotinidase deficiency.

Therefore, biotinidase deficiency should be diagnosed early and treated with biotin supplements. If treated with biotin at prescribed pharmacological doses, serious abnormalities can usually be prevented.

Is biotinidase deficiency linked to problems during pregnancy?

Because biotinidase deficiency is a genetic disorder, it has no direct relationship to pregnancy. A genetic condition, biotinidase deficiency results from a genetic mutation inherited from a parent. This condition results from the incorrect transmission or alteration of genetic material.

Problems experienced during pregnancy are often associated with conditions that arise from non-genetic, external factors. Because biotinidase deficiency is a genetic disorder, it can put a child at risk if either parent carries the genetic condition.

Therefore, pregnancy-related complications are generally due to nongenetic factors, and genetic conditions such as biotinidase deficiency are not directly linked to this process. However, if there is a family history of such genetic conditions, genetic counseling and prenatal screening can help assess this risk.

What causes biotinidase deficiency in babies?

Biotinidase deficiency in infants is usually a genetic condition. This condition is caused by a mutation in the BTD gene, which regulates the activity of the biotinidase enzyme. The biotinidase enzyme regulates the body's interaction with the vitamin biotin, making it available for use. This vitamin is essential for the body to metabolize fats, proteins, and carbohydrates.

Biotinidase deficiency occurs when one or both parents carry this genetic mutation. The condition is inherited in an autosomal recessive manner. If both parents are carriers, there is a risk of biotinidase deficiency in any pregnancy.

Biotinidase deficiency in infants begins to show symptoms at birth, and early diagnosis and treatment are crucial. Newborn screening tests are used to identify infants with biotinidase deficiency at an early stage. Treatment involves lifelong biotin supplementation. This treatment is essential for maintaining biotin levels in the body and supporting normal metabolic functions.

Biotinidase deficiency and the importance of genetic screening

Genetic screening is important to assess the risk of genetically transmitted diseases such as biotinidase deficiency and to identify carrier status. Biotinidase deficiency has an autosomal recessive inheritance pattern, increasing the likelihood of an affected child if both parents are carriers.

It's important to assess the carrier status of each parent and seek genetic counseling for each pregnancy. Genetic screening tests can determine whether parents are carriers, and this information can help couples understand their risk.

If both parents carry the biotinidase deficiency gene, their children will be at risk for the condition. In this case, genetic screening can help at-risk couples consider options such as prenatal testing and preconception carrier testing for individuals who are carriers. This information can guide families toward appropriate genetic counseling and treatment options.

Recommendations for those with babies with biotinidase deficiency

• Regular checkups: Children should attend regular appointments with a pediatrician or a pediatric metabolic specialist. These checkups evaluate the child's general health, growth, and development.
• Eye and hearing checkups: Annual eye and hearing checkups are important for early detection of visual or auditory problems that may occur due to biotinidase deficiency.
• Meeting with a geneticist: Families can learn about genetic risks and family planning by meeting with a geneticist. These specialists can provide genetic counseling and help families make decisions about future pregnancies.
• Communication with different clinical specialists: If a child has different clinical issues, they should be in regular contact with relevant specialists. For example, specialists such as a dermatologist, neurologist, or dietitian can provide assessments tailored to the child's specific needs.
• Taking supplements regularly: They should take their prescribed biotin supplements regularly. These supplements can help the body process biotin due to biotinidase deficiency.
• Lifelong adherence to treatment: It's important to remember that biotinidase deficiency is a lifelong condition. Regular treatment attendance is critical to ensuring a healthy child's life.

Each child's situation may vary, so treatment and recommendations tailored to their specific situation should be followed. Families should work closely with healthcare professionals to ensure a positive impact on their child's health.

Can biotinidase deficiency be diagnosed before birth?

Prenatal diagnosis is possible for at-risk pregnancies and can be performed by enzymatic analysis or, when the mutation is known, mutation analysis. However, such genetic testing is not generally part of routine prenatal screening programs. Biotinidase deficiency is a genetic disorder, and if one parent is a carrier, the condition can occur in a child.