Biotinidase deficiency is a very rare inherited metabolic disorder. It occurs due to a genetic defect in the enzyme biotinidase. About one in 80,000 children is born with such an enzyme disorder. Newborn screening helps to make the diagnosis.
What is biotinidase deficiency?
Biotinidase deficiency, or BTD for short, belongs to the group of rare inherited diseases. Like almost all metabolic diseases, the enzyme defect is inherited in an autosomal recessive manner. This means that both parents are carriers of the disease but do not suffer from it themselves. Biotinidase deficiency is caused by mutations in the BTD gene, which is located on chromosome 3. It was not until the 1980s that the biotinidase defect was discovered as the trigger for this rare metabolic derangement. Biotinidase is an enzyme. It has the task of processing the free biotin contained in the chemical compound biocytin, which is not bound to a protein, so that it can be utilized by the organism. This is important both in the recycling of biotin in the body and in the absorption of biotin through food.
Causes
If the enzyme is unable to do this work or does it inadequately, the biocytin is lost through the kidney. With the result that biotin stores in the body are reduced over time, even if sufficient biotin is taken in with food. Thus, a biotinidase deficiency develops over time. Two forms of BTD are distinguished. The severe biotinidase deficiency, which has an enzyme activity of less than ten percent. And the partial deficiency, which still brings it to an enzyme activity of ten to 30 percent. Biotin, formerly known as vitamin H or skin vitamin, is important for fatty acid metabolism, influences cell growth and is responsible for the formation of glucose. The effects of BTD deficiency are severe and primarily affect organs with a high metabolic intensity. These include the brain, muscles, and immune system.
Symptoms, complaints, and signs
Consequences of biotinidase deficiency include seizures, developmental delay, hearing loss, lack of muscle tone, ataxia, degenerative disease of the optic nerve, and respiratory problems. Symptoms develop gradually from infants to toddlers. They can occur over the course of two weeks to three years.
Diagnosis and course
Because four important enzymes are affected in a biotinidase defect, symptoms vary widely from patient to patient. Also, not every symptom occurs in every child. Therefore, a biotinidase deficiency must be diagnosed as soon as possible in order to be able to treat it. In Germany, a corresponding examination has been part of newborn screening since 2005, the costs of which are borne by the statutory health insurance funds. If BTD is suspected, a photometric biotinidase test can be used to detect the metabolic disease. For this purpose, a blood analysis of newborns is essential. This is done on the third day of life by means of a blood sample, which is usually taken from the baby’s heel, more rarely from the vein. The blood is spread evenly on a filter paper card and dried for one hour at room temperature. After that, the sample goes to the laboratory. However, this first test does not give a definitive diagnosis. This is because abnormal blood values are relatively common in infants. This is particularly the case with premature infants, febrile episodes or during penicillin treatment. In addition, the symptoms of BTD are similar to those of other metabolic diseases. To be completely sure, a new blood test is performed five days later. But even then, it is still not entirely certain which metabolic disease is really involved. This is because the genes on chromosome 3 are also associated with other genetic diseases. More than 60 mutations are known to cause an enzyme defect. Therefore, a genetic test is still used. This genetic analysis is used to confirm the blood diagnosis.
Complications
A wide range of complications can occur as a result of biotinidase deficiency. Depending on the severity of the disease, for example, movement disorders such as ataxia, hypotonia, or spastic paresis occur as a result of the deficiency. In addition, the risk of epilepsy-like seizures, infections and inflammations such as dermatitis or conjunctivitis increases.This can lead to loss of appetite, weakness and fatigue, as well as hair loss and severe disorders of the immune system. In addition, hearing loss and eye damage such as retinal degeneration or visual field impairment often occur. In advanced stages, biotinidase deficiency can cause further complications. If partial biotinidase deficiency is present, atopic or seborrheic dermatitis often occurs in the course of the disease. In addition, flu-like infections usually occur, which, in conjunction with the already weakened immune system, can lead to serious consequences such as heart attack or circulatory collapse. Rarely, organ failure occurs as a result of the deficiency, leading to the death of the patient. Complications of the hereditary disease usually occur shortly after birth and can lead to severe brain damage, coma and death. Severe consequences of this type can be prevented by lifelong treatment with biotin.
When should you see a doctor?
As a rule, a doctor should be consulted immediately in case of biotinidase deficiency to avoid complications and other late effects. In most cases, biotinidase deficiency is manifested by seizures associated with severe pain. Therefore, if these seizures or epileptic seizures occur for no particular reason, a doctor must be consulted in any case. Slow hearing loss and disturbances and delays in development may also indicate a biotinidase deficiency and should be examined by a medical professional. In many cases, those with biotinidase deficiency also suffer from vision loss and respiratory problems. The complaints and symptoms are gradual in this disease and usually do not occur suddenly. For this reason, regular examinations by a doctor are necessary, especially in children, in order to avoid complications. As a rule, a general practitioner can be consulted if a biotinidase deficiency is suspected. A blood analysis can determine the biotinidase deficiency so that treatment can also be initiated. If there are psychological complaints in the parents or relatives, a psychologist should also be consulted.
Treatment and therapy
Although the disease cannot be cured, since its cause is genetic. But the prognosis is very good if therapy is started before the first symptoms appear and if it is carried out consistently. The treatment is simple and consists of the daily administration of a biotin tablet, but this must be done for life. Patients are closely monitored in a special metabolic center. This includes regular monitoring of the metabolism, as well as checks of the eyes and hearing function.
Outlook and prognosis
Biotinidase deficiency basically has a poor chance of cure. The genetic disorder is considered incurable. Legal requirements prohibit doctors, researchers and scientists from actively interfering with human genetics. Nevertheless, thanks to medical progress, a very good treatment method has been found. With timely drug treatment, the patient is free of symptoms for life. In order to achieve and maintain this state of health, a comprehensive examination must be initiated at an early stage. The sooner a diagnosis is made, the sooner therapy can begin. This consists of taking a medication every day. This is a long-term therapy and the drug must not be discontinued. Alternatively, the symptoms would return within a short period of time. By taking one biotin tablet a day, the patient can live symptom-free for the rest of his or her life. Without medical treatment, the patient is threatened with various secondary symptoms of the disease. These are manifold and have very different degrees of severity. In rare cases, a weakened immune system can lead to a heart attack or a circulatory collapse. Epileptic seizures can occur, which represent an immense interference is the well-being and quality of life in everyday life. Supportively, sufficient foods with vitamin B7 can be consumed for the maintenance of health.
Prevention
The success of treatment of biotinidase deficiency is determined by timely therapy before the onset of symptoms. This is where intensive education of families plays a role in helping them understand the urgency of treatment.Without therapy, the disease leads to lasting damage. These include malfunctions of the immune system, life-threatening metabolic disorders, and brain damage that can lead to coma or even death of the child. Therefore, the time of the beginning of the therapy is of eminent importance. The earlier, the better the chances of the young patients. If a child already shows developmental delays, hearing impairment or incipient degeneration of the optic nerve, there is a risk that they cannot be reversed even by biotin therapy. Otherwise, however, patients can expect a completely normal life with biotin therapy. Only raw eggs should be avoided. These contain avidin, a glycoprotein that can bind biotin. Cooked eggs, on the other hand, in which avidin is no longer active, are not dangerous. Treatment with biotin is completely free of side effects.
Aftercare
Biotinidase deficiency must be treated throughout life. Follow-up care focuses on regular screenings and adjusting medication to the ever-changing symptom picture. Developmental deficits that could not be compensated during the course of therapy must also be treated with medication and behavioral therapy as part of follow-up care. Although this usually does not lead to an improvement in the state of health, further progression of the disease can often be prevented. In addition, aftercare focuses on enabling the patient to lead a life relatively free of symptoms. This is achieved by organizing appropriate aids for any physical disability at an early stage. In the best case, the skin and metabolic symptoms regress completely. Here, follow-up care focuses on regularly checking whether a recurrence has formed or unusual symptoms occur that require further observation. If these measures are reliably followed, patients suffering from biotinidase deficiency can lead a relatively symptom-free life without further complications. Parents often need to seek therapy after the initial treatment, as raising an affected child may involve tremendous physical and emotional effort.
Here’s what you can do yourself
Biotinidase is a very important enzyme for metabolism and the immune system because it can dissolve the contained biotin from biocytin, which is also known as vitamin B7. Vitamin B7 performs important cross-sectional functions in every cell nucleus and plays a key role in carbohydrate, protein and fat metabolism. A deficiency of biotinidase leads to a deficiency of biotin. It is very important that the rare hereditary disease that causes biotinidase deficiency is diagnosed as early as possible – shortly after birth – in order to compensate for the biotin deficiency via lifelong oral intake with a daily tablet. Early diagnosis is so important because biotin deficiency can cause serious metabolic damage that is irreversible. Adaptation to everyday life and self-help measures are unnecessary because the daily intake of just one biotin tablet is associated with a normal life expectancy without any lifestyle restrictions. An unintentional overdose is completely harmless because the metabolism can continue to metabolize the biotin without any problems in the event of an oversupply. It is recommended to carry a sufficient supply of biotin tablets when traveling abroad and especially when traveling long distances, in order not to have to interrupt the intake of biotin, which could be associated with serious and severe consequences after a short time.
