Screening of 58 neonatal metabolic disorders in Iran (Part 7 - Biotinidase deficiency)

Screening of 58 neonatal metabolic disorders in Iran (Part 7 - Biotinidase deficiency)


Following the previous discussion, we will examine another disorder that is being screened in this test, namely the deficiency of the enzyme biotinidase.

Biotinidase deficiency

Lack of the enzyme biotinidase is a rare congenital metabolic disease that, if diagnosed early in life, can be easily treated and will prevent permanent mental and physical retardation.

- The hereditary pattern of this disorder is autosomal recessive, ie it is observed in girls and boys equally. That's why they are more common in consanguineous marriages.

Biotinidase is an important enzyme in the body. Enzymes are special proteins that the body needs to digest food and make some fats and sugars. Biotinidase helps the body absorb and reuse the biotin in food.

The presence of biotin is very important for the health of the skin, hair, bone marrow and nervous system.

The enzyme biotinase releases biotin from proteins in the diet or during the return of body proteins.

The disease is classified as multiple carboxylase disorders. The presence of biotin as a cofactor is essential for the activation of carboxylase enzymes in the body, so after the binding of biotin to the amino acid lysine in carboxylase enzymes (apocarboxylase), the above enzymes are activated and this active form is called holocroboxylase.

Following the breakdown of carboxylase enzymes in the body, biotinyl-lysine is produced. The resulting biotin-lysine (Biocytin) is released by the enzymes biotinidase, hydrolysis, and biotin, which can be re-available to the decomposed carboxylase enzymes.

Therefore, in people with biotinidase deficiency, the body's biotin is reduced, which leads to a decrease in the activity of carboxylase enzymes. As a result, there are problems with gluconeogenesis, the production of fatty acids, and the catabolism of amino acids (due to the role of carboxylase in them).

Biotin is one of the B vitamins and acts as a coenzyme in the metabolism of fatty acids, carbohydrates and amino acids, as well as the synthesis of vitamins B6 and B12.

It contains a nucleus of imidazole and is found in whole grains, liver, eggs and milk (also called vitamin B8 or vitamin H).

 

Clinical signs:

- Birth time: normal.

Infancy, infancy, or childhood: The onset of symptoms may vary depending on the amount of biotin received, as well as the activity of the enzyme biotinidase, from the first few weeks before birth or a few years after birth. She is 6 months old.

Depending on the activity of the enzyme biotinidase, the disease is seen in two forms: severe deficiency (enzyme activity less than 10%) and relative deficiency (enzyme activity between 10 and 30%).

 In most cases, the first manifestation of the disease is in the form of skin symptoms or seizures. Skin lesions are usually scattered, but the entire skin may become red and scaly. These lesions are associated with cracks around the pores of the body (such as cracks in the corners of the lips).

Severe inflammation of the eyelids, conjunctiva and cornea can also be seen. Dermatitis (seborrheic) may also be present. There is often skin-mucosal candidiasis and immunodeficiency of B and T lymphocytes. Alopecia (alopecia areata) is common in the scalp, eyebrows, or eyelashes at birth or during infancy.

 Recurrent attacks of acidosis, ketosis, and organic acidosis also occur, with a decrease in temperature, a sharp decrease in muscle tone, a lack of tendon reflexes, and coma. Acid attacks may occur during an acute infection.

Neurological symptoms are a major manifestation of the disease and include an imbalance that can prevent walking. Other symptoms include tremors or tremors, which may be the only manifestation of the disease.

 Spasm or muscle cramps in infancy, developmental delay, noisy breathing or shortness of breath and apnea, Bulbar's paralysis (progressive conjunctival paralysis caused by gradual damage to the lower part of the brainstem, and a person with complications such as swallowing, speech and atrophy Tongue muscles are affected) are seen in these patients.

Late-onset symptoms include neurosensory impairment of the optic and auditory nerves, which can lead to severe myopia and deafness.

Childhood and Adolescence: Spastic weakness of the lower limbs, progressive atrophy of the optic nerve, and acute blindness following acute infectious diseases.

Notes:

In any patient with seizures without explanation, the enzyme biotinidase should be evaluated.

In the differential diagnosis of acrodermatitis entropatica (a rare genetic disease that is inherited as a defeated autosomal recessive disorder).

 Serum levels in these patients are usually low and occur as skin lesions, especially in the prefrontal cortex as well as the limbs, along with hair loss and diarrhea) and ectodermal dysplasia of the biotinidase enzyme deficiency should be considered.

Ectodermal dysplasias are a genetic and inherited disease in which hair, nails, sweat glands and teeth are found to be defective. When a person has at least two of these types of abnormal ectodermal features - for example, deformed teeth with extremely low back hair - it is considered to have ectodermal dysplasia.

In any patient with lactic acid deficiency, the enzyme biotinidase should be evaluated.