What is Biotinidase Deficiency? Symptoms, Diagnosis, and Treatment

Biotinidase deficiency is an inherited metabolic disorder characterized by an impairment in the body's ability to utilize biotin, one of the B-complex vitamins. Biotin is of vital importance as a cofactor for carboxylase enzymes involved in the metabolism of fatty acids, amino acids, and glucose. The biotinidase enzyme, in this process, releases protein-bound biotin, enabling its absorption from the intestines. If biotinidase deficiency is not diagnosed, particularly in the neonatal period, it can lead to serious complications such as cognitive impairment, hearing loss, skin problems, and even coma. The symptoms of the disease can be significantly controlled with oral biotin supplement therapy, which is started early and continued for life.

What is Biotinidase Deficiency?

Biotinidase deficiency is a rare autosomal recessive metabolic disorder that causes the body to lose its ability to reuse biotin, a type of B-complex vitamin also known by other names such as vitamin B7 or vitamin H. Normally, the human body recycles biotin several times to keep it available for carboxylase enzymes. However, in the bodies of individuals with biotinidase enzyme deficiency, biotin cannot be recycled for reuse. As a result, vital processes such as energy production metabolism, fatty acid synthesis, and amino acid metabolism can be negatively affected.

Biotin, which originates from the Ancient Greek word "biotos" meaning life, plays a role in many vital processes, from the healthy development of the fetus to the protection of skin, hair, eye, liver, and nervous system health, as its etymological origin suggests. Because the bodies of individuals with biotinidase deficiency cannot utilize biotin as they should, a condition known as biotin deficiency emerges.

According to some studies, biotinidase deficiency is more common in populations where consanguineous marriages are frequent. The main reason for this is that biotinidase deficiency is a health problem transmitted via autosomal recessive inheritance. In other words, the transmission of faulty genes from both the mother and the father is the primary cause of the disease. The flow chart of biotinidase deficiency is examined in two categories according to the degree of deficiency. Accordingly, biotinidase deficiency is classified as follows:

Profound biotinidase deficiency: A condition where enzyme activity is less than 10% and symptoms are severe.

Partial biotinidase deficiency: A condition where enzyme activity is between 10–30% and symptoms are milder.

If biotinidase deficiency in an infant is not diagnosed early and appropriate treatment is not started, serious complications ranging from neurological problems to vision loss may develop.

What Are the Symptoms of Biotinidase Deficiency?

Biotinidase enzyme deficiency leads to the impairment of the functions of certain biotin-dependent enzymes due to the body's inability to reuse biotin. Because the insufficient functioning of these enzymes disrupts basic metabolic processes such as energy production and nervous system operation, serious complications can arise in the case of biotinidase deficiency. Symptoms appear in the first weeks or months after birth, especially in cases of profound deficiency where biotinidase deficiency levels are below 10%.

Biotin is one of the important micronutrients that contributes to the normal functioning of the nervous system. For this reason, if there is a health problem such as biotinidase enzyme deficiency that affects the use of biotin in the body, significant effects can be seen, especially on the nervous system. If the disease is not treated early, the immune system in infants weakens, and energy production metabolism and nerve conduction are disrupted.

Accordingly, the main symptoms of biotinidase deficiency can be listed as follows:

Low muscle tone, also known as floppy infant syndrome,

Feeding problems such as loss of appetite, which may be accompanied by vomiting, and refusal to eat,

Respiratory system problems such as rapid breathing, sleep apnea, and wheezing while breathing,

Developmental delay,

Lethargy characterized by extreme fatigue, unresponsiveness, and constant sleepiness,

Ataxia characterized by difficulty in controlling muscle movements,

Skin rash,

Severe hair loss,

Hearing problems,

Vision problems due to damage to the optic nerve that carries signals from the eye to the brain.

In addition to those listed, there are some studies showing that there may be a significant relationship between biotinidase deficiency and epilepsy.

What Causes Biotinidase Deficiency?

Biotinidase deficiency is an autosomal recessive inherited metabolic disorder caused by a mutation in the gene called BTD. In other words, for the disease to occur, a faulty BTD gene must be transmitted from both the mother and the father. Studies show that the risk of transmitting biotinidase deficiency to their children for couples who are both carriers is approximately 25%.

The biotinidase enzyme is the primary enzyme in the body that enables the recycling of biotin (vitamin B7). Normally, biotin is taken from food in free form or as protein-bound biotinyl-peptides. While free biotin can be used directly, protein-bound biotin must be separated and made free via the biotinidase enzyme to be used by the body.

A mutation in the BTD gene causes the biotinidase enzyme to either not be produced at all or to be produced in a non-functional form. As a result, free biotin cannot be added to the biotin pool. Furthermore, impairment is observed in the activity of various biotin-dependent enzymes. The inability of these enzymes to perform their functions as they should leads to impairment in amino acid, fatty acid, and carbohydrate metabolism.

The impairment in the use of macronutrients is not the only reason these enzymes cannot perform their functions. One of the primary tasks of biotin is to participate in the metabolism of normal macronutrients. If biotin cannot be used in the body as it should be for various reasons, impairment in the metabolism of macronutrients such as fat, protein, and carbohydrates, and disruptions in normal energy production may be observed.

How Is Biotinidase Deficiency Diagnosed?

Biotinidase deficiency can be easily detected with the help of screening tests performed in the neonatal period. Today, thanks to diagnostic methods such as taking a heel prick blood sample from infants, the activity of the biotinidase enzyme can be measured. For the diagnosis of biotinidase deficiency, the biotinidase enzyme activity in serum or plasma is first measured. In case of a significant decrease in enzyme activity, specialists may request genetic tests for the BTD gene to confirm the diagnosis. With this biotinidase deficiency screening test, it can be evaluated whether there is a mutation in the BTD gene.

In addition to these, in some cases, specialists may resort to diagnostic methods such as measuring lactic acid and ammonia levels in blood or urine, checking arterial blood gas, serum amino acid analysis, and serum biochemistry tests to confirm the diagnosis.

How Is Biotinidase Deficiency Treated?

The earlier the treatment for biotinidase deficiency begins in infants, the better. Specialists consider biotinidase deficiency to be one of the most fortunate hereditary diseases. The main reason for this is that although it needs to continue for life, the treatment process is quite simple. The basis of the treatment is oral biotin (vitamin B7) supplementation. While specialists usually prescribe 5 to 20 mg of biotin supplementation initially, the treatment dose can be increased up to 40 mg in some patients.

If the treatment process for biotinidase deficiency is started before symptoms appear, permanent damage such as neurological problems, hearing loss, and vision loss can be prevented. However, it is also possible to prevent the progression of damage with treatment in individuals who already have irreversible damage.

Frequently Asked Questions

Biotinidase deficiency is an autosomal recessive inherited disease, meaning it is passed on by the transmission of faulty genes from the mother and father. In other words, the disease is not acquired later; it is congenital. Biotinidase deficiency can be detected early today thanks to newborn screening tests applied in most countries. Within the scope of newborn screening tests, the activity of the biotinidase enzyme is measured with a few drops of blood taken from the infant. If the enzyme activity is found to be low, whether there is a mutation in the BTD gene can be investigated with genetic tests for a definitive diagnosis. Biotinidase deficiency requires a lifelong treatment procedure. However, oral biotin supplementation helps to control symptoms. If treatment is delayed, serious complications may develop in patients. Especially because brain development is affected, complications such as neurological problems, permanent hearing loss, and vision loss may occur. Although it is not accurate to say clearly that biotinidase deficiency directly causes intellectual disability, in cases where treatment is not started early, problems such as a decrease in cognitive functions, learning difficulties, and attention problems may be observed. Due to delayed treatment, seizures may initially be seen in the majority of patients with biotinidase enzyme deficiency. However, after starting treatment, seizures usually disappear on their own. Since there is no definitive method for the treatment of biotinidase enzyme deficiency, biotin supplementation must be used for life. Biotinidase deficiency can be detected shortly after birth today thanks to newborn screening tests that are routinely performed in many countries. If a suspicious finding is detected as a result of the screening, specialists may resort to detailed genetic analysis. If parents are only carriers, they usually do not show any symptoms. However, the risk of parents who are both carriers transmitting the disease to their children is approximately 25%. For this reason, it may be beneficial for expectant parents who are known to be carriers to receive genetic counseling before pregnancy.

Biotinidase Deficiency Can Be Controlled with Early Diagnosis

Biotinidase deficiency is one of the rare metabolic diseases that can be controlled with a simple treatment continued for life when diagnosed early. Thanks to newborn screenings and genetic evaluations, it is possible to prevent potential complications.

Our Hisar Hospital Intercontinental Department of Pediatrics and Pediatric Health provides services with a multidisciplinary approach in the diagnosis and treatment of hereditary metabolic diseases, especially biotinidase deficiency.

You can make an appointment with our specialist physicians to get detailed information about early diagnosis and the correct treatment plan for your baby's health.