Introduction:
TRNT1 (CCA-adding transfer RNA nucleotidyltransferase) deficiency is a rare disorder; only a few cases have been reported till now. TNRT1 deficiency is genetically inherited as an autosomal recessive trait. This means that the parents of the affected individual have single copies of these genes and act as carriers without showing any signs and symptoms. Most of the cases with TRNT1 deficiency die before they reach adolescence. Most of the people with this deficiency have undergone allogeneic bone marrow transplantation and have survived with this deficiency. However, a person's survival rate or the average life expectancy of TRNT1 deficiency ranges between 10 months to 14 years.
What Are the Causes of TRNT1 Deficiency?
The TRNT1 gene is involved in making proteins by giving directions to the proteins. Generally, during protein synthesis, tRNA (transverse ribonucleic acid) helps organize the amino acids, which are considered building blocks of proteins. Every tRNA transports one particular amino acid for protein chain formation. TRNT1 helps correct and properly attach each tRNA to amino acids.
When TRNT1 gene mutation occurs, it leads to the deficiency of TRNT1, thereby hampering its function. As a result, the TRNT1 gene misses the command over tRNA, and the tRNA is less likely to participate in protein synthesis. Studies show that protein synthesis takes part in the mitochondria, which are considered powerhouses of the cells. Hence, the reduced energy output may destroy and damage various cells and their structures in the body. Genetic testing helps in the diagnosis of TRNT1 deficiency.
What Does TRNT1 Deficiency Cause?
TRNT1 deficiency could lead to a group of disorders affecting different parts and systems of the human body. TRNT1 deficiency will show its effects on the eyes, blood, immune system, and nerves. However, there may be wide variation in signs and symptoms. The following are the disorders caused due to TRNT1 deficiency:
1. Sideroblastic Anemia: Sideroblastic anemia is a blood disorder that affects the RBC (red blood cells). Sideroblastic anemia causes anemia (a decrease in the number of red blood cells) and iron overload. In this condition, the red blood cells show morphological variations (decrease in the size of red blood cells), and the newly formed red blood cells in the bone marrow show an unusual build-up of iron. Sideroblastic red blood cells have an abnormal build of iron around the nucleus of the blood cells. When observed under a microscope, the abnormal iron ring in the center of the cell takes up the blue dye and appears as a blue ring around the nucleus. Hence, these cells are called ringed sideroblasts.
The presence of iron rings is an indication that the red blood cells are storing the iron instead of utilizing it. If a person is suffering from sideroblastic anemia, it means their body cannot use iron. This will show its impact in two ways:
Decreased oxygen supply throughout behind the unused iron piles up in the bone marrow, which causes abnormal production of ringed sideroblasts. And this excess amount of unused iron is responsible for many health complications.
2. Immunodeficiency: TRNT1 deficiency will show its impact on the body's immune system. The immune system becomes weak, and the body is more prone to recurrent infections (bacterial, viral, and parasitic). Frequent bacterial infections cause damage to many internal organs of the body, thereby leading to life-threatening conditions. TRNT1 deficiency will affect the B cells of the immune system. Most of the immune cells are found in blood circulation. White blood cells take care of the body's defense mechanisms. The white blood cells are distinguished into B cells and T cells.
T lymphocytes protect the body from harmful microorganisms. B cells, also B lymphocytes, produce proteins known as immunoglobulins (antibodies). These antibodies attack the foreign substances entering the body and engulf (eat) them. Thus, B lymphocytes play a crucial role in the body's defense mechanism. In individuals with TRNT1 deficiency, antibody production is decreased. Therefore, the protection mechanism is lost, and the body is prone to persistent infections.
3. Retinitis Pigmentosa: TRNT1 deficiency can lead to progressive loss of vision. The eyes consist of a light-sensing sensitive layer called the retina present at the back side of the eyeball. The retina comprises layers of nerve tissue; this retina captures pictures and processes them as electric signals to the brain with the help of the optic nerve. TRNT1 deficiency will gradually lead to the destruction and damage of the light-sensing retina, which will lead to eye abnormalities.
The symptoms initially appear as diminished vision at night or in dim light and then slowly progresses, leading to central and peripheral vision loss. There are no treatments that resolve retinitis pigmentosa effectively. Wearing sunglasses may conserve vision.
4. Fevers: TRNT1 deficiency can cause recurrent fevers, and the cause of these fevers is not because of the infections (bacterial, viral, and parasitic). These periodic fevers are one of the earliest signs of TRNT1 deficiency. They mostly attack children causing vomiting, diarrhea, and loss of appetite. The condition can sometimes be fatal and require hospitalization. These fevers occur repeatedly, once every two to four weeks, and require a hospital stay of five to seven days. However, these episodes and the intensity of fevers decrease as the child grows.
5. Neurological Abnormalities: People with TNRT1 deficiency develop certain neurological problems like delayed speech and motor (movement) development skills such as walking, sitting, and standing. Decreased muscle tone, called hypotonia, is usually seen in TRNT1-deficient people.
6. Other Problems: People with TRNT1 deficiency can also encounter other problems like deafness (loss of hearing), repeated fits (seizures), and kidney and heart abnormalities.
What Are the Other Names for TNRT1 Deficiency?
TNRT1 deficiency is also called by other names such as:
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SIFD (sideroblastic anemia, immunodeficiency, fevers, delayed neurological development).
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RPEM (retinitis pigmentosa with erythrocytic microcytosis).
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TRNT1 enzyme deficiency.
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TRNT1 protein deficiency.
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Immunodeficiency related to TRNT1.
Conclusion:
TRNT1 deficiency can lead to a spectrum of disorders. They appear as mild conditions during childhood, such as fevers, and as age increases, the TRNT1 deficiency will affect the other systems in the body, causing sideroblastic anemia, retinitis pigmentosa, and immunity disorders like fevers. Bone marrow transplantation is considered to be beneficial in people suffering from sideroblastic anemia and immune disorders with no recurrent infections.
