in different countries, based on the national program of each country, from two to more than 50 diseases are included in the screening list of metabolic disorders. Currently, in our country, only two congenital hypothyroid diseases and PKU are included in the national screening program for neonatal metabolic disorders.
In addition to these two diseases, this center, as the first and only center in the country, can treat six diseases (congenital hypothyroidism, phenylketonuria, galactosemia, biotinidase deficiency, congenital adrenal hyperplasia, cystic fibrosis) using modern technologies (AutoDELFIA and Victor). , G6PD deficiency) mentioned in the screening of newborns that cannot be identified by the TMS method.
It should be noted that the results related to this measurement method only indicate the probability of the disease and additional confirmatory tests must be performed for confirmation.
It should be noted that hereditary and genetic diseases detected by this test are not 100% curable in all cases and in some of them only the severity of symptoms and complications can be reduced. On the other hand, the normality of this test does not guarantee that the child will not be infected in the future, because mild cases of hereditary diseases may have a normal screening test. Despite all these shortcomings and problems, currently, the best way to prevent future serious irreparable injuries in children all over the world is through newborn screening tests.
Congenital hypothyroidism (CH)
The thyroid gland secretes thyroid hormones that are responsible for controlling the body's metabolism and the physical and brain development of the baby.
Congenital deficiency of these hormones, if not diagnosed and treated in time, causes severe physical and brain growth retardation and mental retardation in the child.
Most of the patients are asymptomatic in infancy and symptoms may start within a few weeks. Only 5% of babies are symptomatic from the beginning. The symptoms of the disease can be in the form of prolonged jaundice, swelling around the eyes and facial puffiness, cold and dry skin, large tongue, umbilical hernia, enlarged temples, paleness, excessive sleepiness, lack of crying or violent crying, decreased Frequency of breastfeeding, constipation, muscle weakness, slow growth, especially growth around the head. Also, one-third of babies with congenital hypothyroidism are born late (more than 42 weeks).
The screening test in most countries is by measuring the TSH hormone. Its amount in babies is different depending on the gestational age and birth weight. Decisions about TSH levels that require treatment vary based on screening programs in each country. It should be noted that the increase in TSH level in heel blood drop should be confirmed with additional tests in venous blood. With the screening test before symptoms and brain damage appear, the affected baby can be diagnosed and levothyroxine tablets can be prescribed to prevent irreparable brain damage in the future. Treatment should start within three weeks.
The early start of treatment is associated with higher IQ, and the later the treatment starts, the greater the drop in IQ.
Galactosemia
Galactose is a sugar found in milk, which is converted into glucose in the body during a metabolic process, which is an important source of cellular energy. In a patient with galactosemia, this conversion is not done due to enzyme deficiency, and the baby suffers from severe hypoglycemia, convulsions, blood infection, frequent vomiting, prolonged jaundice, liver enlargement, and failure, coagulation problems, cataracts, brain damage, and coma. To prevent the mentioned side effects, the consumption of galactose is stopped. Therefore, the consumption of mother's milk or conventional milk powders should be stopped immediately in the affected baby and galactose-free dietary milk should be replaced for the baby. In this case, the baby will be protected from brain, liver-kidney, and eye damage. If a baby has a history of blood transfusion, it should be three months after the blood transfusion and then the enzyme test should be done.
Three enzymes are involved in the metabolism of galactose to glucose, and the deficiency of any of these enzymes causes galactosemia, and the most important of them is the GALT enzyme, and its deficiency causes the classic and severe form of galactosemia. Of course, a mild type has also been reported, in which the level of enzyme activity is slightly reduced, and this form does not require treatment. The prevalence of galactosemia is 1/30,000 to 1/60,000. In the newborn screening test, the concentration of galactose and galactose 1-phosphate in red blood cells is quantitatively measured by the immunofluorescence method, and the deficiency of each of the three enzymes in the pathway of galactose metabolism increases the concentration of the above values. The confirmatory test for this disease is the measurement of the enzyme related to the conversion of galactose to glucose (GALT enzyme) in red blood cells and genetic testing to find disease-causing mutations. Genetic testing can find gene mutations in 99% of cases. An enzyme test is usually enough to confirm the disease and there is no need for a genetic test except in cases where the intention is to get pregnant again and perform the prenatal test (PND). The inheritance of this disease, like many other metabolic diseases, is autosomal recessive and both parents have a defective gene and carry the disease. Boys and girls have the same chance of getting the disease. The probability of disease in the next pregnancy is 25%. There is a 50% chance that the next child will be a carrier of the disease like the parents and 25% will be completely healthy. The treatment of the disease is to eliminate all sources of lactose (galactose+glucose) and galactose, which are mainly found in dairy products. Some fruits and vegetables also contain galactose, which should be limited. The only permitted milk is soy milk which does not contain galactose and hydrolyzed casein milk which contains small amounts of galactose. The diet should be continued until the end of life to prevent complications.
Biotinidase deficiency
Biotin is one of the B vitaminsis that plays a complementary role in the activity of many body enzymes and plays an important role in protein, fat, and carbohydrate metabolism. The biotinidase enzyme turns this vitamin into an active form and completes its cycle in the body. Deficiency of this enzyme is associated with symptoms such as seizures, muscle weakness, immune system defects, blindness, deafness, skin problems, skin fungal infections, hair loss, and mental retardation. The prevalence of the disease is about 1/60,000 and it is more common in the Middle East. The disease can be seen in two forms: mild (10-30% enzyme deficiency) and severe (less than 10% enzyme deficiency). The enzyme is measured semi-quantitatively in a drop of blood from the heel by the immunofluorescence method, by detecting enzyme deficiency in a screening test and timely treatment with biotin in a high dose, the symptoms can be prevented and the baby will grow and develop normally.
Symptoms of the disease usually start at 3-6 months of age and usually involve the nervous system and skin. Seizures, delayed development and mental retardation, peeling, eczema, hair loss or baldness, blindness, deafness, imbalance, respiratory problems, enlarged liver, and spleen, and increased blood acid, and ammonia is among these symptoms. In mild forms, neurological symptoms may not be seen and only skin symptoms may be present. Sometimes it is completely asymptomatic and it is not detected until adulthood. In the severe form of the disease, there may be abnormal metabolites in the blood and urine in the heel blood test by the TMS method and other complementary tests, but it is not always, that is why it is necessary to Examination of the enzyme in the blood of the heel. A confirmatory test should be done by measuring the enzyme on fresh blood in a quantitative way. The treatment of the disease is very simple and cheap, and it is possible only by taking a high dose of biotin tablets (2-5 mg per day). In mild forms, 1-5 mg per day is sufficient. The treatment should be started before the appearance of nerve, eye, or hearing symptoms because if these symptoms occur, it is difficult to return them to their normal state. Genetic testing is also available to check for disease mutations but is rarely needed except for prenatal testing (PND) for subsequent pregnancies.
The inheritance of this disease, like many other metabolic diseases, is autosomal recessive and both parents have a defective gene and carry the disease. Boys and girls have the same chance of getting the disease. The probability of disease in the next pregnancy is 25%. There is a 50% chance that the next child will be a carrier of the disease like the parents and 25% will be completely healthy.
Congenital Adrenal Hyperplasia (CAH)
Adrenal hyperplasia or congenital enlargement refers to a group of hormonal disorders of the adrenal gland (adrenal gland) which is caused by the deficiency of 6 enzymes in the gland. The most common enzyme deficiency is related to the enzyme 21-hydroxylase (>90%), as a result of its deficiency, the cortisol hormone, which plays the role of defense against disease and stress and sugar regulation, is reduced and causes hypoglycemia. Also, the increased male sex hormones, as a result, causes confusion in the reproductive system in female babies (bisexual state) and premature puberty in male babies in the future. Also, the lack of this enzyme causes the lack of aldosterone, which is a hormone that balances water and salt and blood pressure, and in some patients (75%) its deficiency is seen, which is associated with excessive excretion of water and salt from the kidney and can cause shock, coma and even death of the baby.
The prevalence of this disease is about 1/15000 per live birth. About 1.5000 has been reported in the Middle East. By measuring the hormone 17-hydroxyprogesterone (17-OHP) by immunoassay method, which increases in these patients, these babies can be diagnosed in the first days of birth and hormonal treatment can be started to prevent fatal complications. In female babies, surgery is needed to correct the external genitalia. Although the screening test does not prevent gender ambiguity, it is also important because it can prevent the misdiagnosis of the baby's gender and wrong naming and the mental and psychological problems caused by it in the family. It should be noted that the amount of this hormone depends on the gestational age and birth weight of the baby, and in premature babies or with low birth weight (less than 2500 grams), its amount is higher than in normal newborns.
The inheritance of this disease, like many other genetic diseases, is autosomal recessive, and both parents have a defective gene and carry the disease, so boys and girls have the same chance of contracting the disease. The probability of disease in the next pregnancy is 25%. There is a 50% chance that the next child will be a carrier of the disease like the parents and 25% will be completely healthy.
Hydroxylase is classified into classical or severe forms with salt excretion (75%), less intense forms without salt excretion (25%), and mild or non-classical forms. In the classic form with salt excretion, the level of the 17-hydroxyprogesterone hormone is usually higher, and 70% of cases can be detected by the screening test. In these patients, the symptoms of gender ambiguity are more severe in female babies, and they usually go into shock and coma following excessive excretion of water and salt, which is fatal if not treated. In the future, premature sexual puberty occurs in male babies and causes premature growth arrest. In male babies, since the external genitalia is normal during the newborn period, if the newborn screening is not performed, the risk of shock and its failure to be diagnosed may increase and the death rate may increase. (5 times compared to normal conditions) In the classical form without excretion of water and salt, the severity of genital ambiguity in female babies is usually less, and there is a possibility of shock and coma only in case of severe stress. Therefore, in the baby boy until the time A child who presents with precocious puberty may not be diagnosed. The secondary increase of ACTH hormone due to the lack of cortisol in these babies causes the skin to be darker than normal, especially in the genital area, gums, knuckles, and nipples. In the non-classical form, a slight increase in the hormone 17-hydroxyprogesterone can be seen and may not be detected in the screening test, and in the future, it may appear with the symptoms of premature puberty or premature acne and hair loss.
The increase in the hormone 17-hydroxyprogesterone in the first 24 hours after delivery is due to the stress of childbirth and should be measured after the second day and finally until the 5-7th day after birth in premature babies, sick babies while they were hospitalized in the NICU and Babies with low birth weight have higher values than normal babies, and it is usually necessary to repeat the test in the coming weeks, so the interpretation of the test results and the need for treatment depends on the discretion of the attending physician. This test has false positives and negatives, and its increase in one time does not mean that you have a disease, and there is a need to perform more complete additional hormonal tests. In mothers who have used coronet during pregnancy for some reason, the 17-hydroxyprogesterone may be normal despite the baby's infection, which should be repeated in 1-2 weeks if the disease is suspected. Also, milder forms may not have a high hormone level in the initial screening test and it needs to be repeated in 1-2 weeks. Today, it is possible to measure 17-hydroxyprogesterone by the TMS method both for the screening test and as a supplementary test. The confirmatory test for definitive diagnosis is the examination of genetic mutations of the 21-hydroxylase enzyme gene.
cystic fibrosis (CF)
Cystic fibrosis is a genetic disease in which the mucous glands have problems in the secretion of chlorine, which is associated with the thickening of mucous secretions and causes involvement of the lungs, digestive system, and sweat glands. The prevalence of this disease in white races has been reported from 1.3500 to 1.7000. Affected patients usually suffer from frequent lung infections and breathing problems. Also, due to the lack of intestinal and pancreatic secretions, digestive problems such as pancreatic insufficiency, malabsorption, constipation, bulky fatty stools, lack of weight gain, and slow growth are severe. In the screening test, the amount of immunoreactive trypsinogen (IRT) is measured by the immunofluorescence method, but its high level does not necessarily mean CF and there is a need for confirmation tests such as a sweat test and an increase in the amount of chlorine, which is possible in the newborn period. It is not acceptable and a genetic test may be required for confirmation. Early diagnosis of this disease in infancy and the initiation of protective and antibiotic treatments can reduce the severity of symptoms and the frequency of lung infections and prevent the patient from slowing down, although there is no definitive treatment for the disease.
Symptoms of the disease appear mainly in infancy, but in about 20% of babies, due to viscous and thick intestinal secretions, they may not pass stool (meconium) in the first days of birth, which raises the suspicion of CF. After this period, the most common symptoms are frequent respiratory infections and growth disorders due to malabsorption secondary to a lack of pancreatic enzymes and intestinal secretions. The infant may suffer from severe protein deficiency due to severe malabsorption. Due to the loss of salt through the sweat glands, the blood salt level may decrease. Usually, the skin of these children tastes salty when kissed. There is a possibility of liver failure, inflammation of the pancreas, and even diabetes in the future. Due to the natural increase of trypsinogen in intestinal secretions during the fetal period, the IRT test may show a false increase, so it is recommended that the test be rechecked 2-3 weeks later, and in case of an increase in the second test, confirmatory tests should be performed. So far, more than 1000 mutations have been identified for the disease, the most common of which is F508 ∆ (70%), and in some countries, a rapid genetic test method for checking common mutations (panel of 25 mutations) is available. If this test is negative, it does not rule out having CF, and other gene mutations should also be checked.
The inheritance of this disease, like many other genetic diseases, is autosomal recessive and both parents have a defective gene and carry the disease. Boys and girls have the same chance of getting the disease. The probability of disease in the next pregnancy is 25%. There is a 50% chance that the next child will be a carrier of the disease like the parents and 25% will be completely healthy.
G6PD deficiency
G6PD deficiency or Glucose-6-phosphate dehydrogenase enzyme or favism is a hereditary blood disease that has no symptoms until exposure to food (such as beans) or certain drugs (such as aspirin, ibuprofen, cotrimoxazole, etc.) or infection. And in case of exposure to these factors, rapid lysis of red blood cells (hemolysis) and severe anemia and its excretion from the kidney, and even kidney failure and death will occur. Symptoms are pallor, jaundice, extreme fatigue, shortness of breath and heart palpitations, and enlarged spleen. The color of urine tends to be dark brown and the amount of urine may decrease due to kidney involvement. This disease is very common in black people and the Middle East. Diagnosis of the disease is done by examining the enzyme by immunofluorescence quantitatively on filter paper. For a confirmatory test, the enzyme can be measured quantitatively in the blood. Genetic testing can also be used, which is usually not necessary. Unlike the previous cases, the inheritance of the disease depends on the X chromosome, which causes boys to be affected and girls to become carriers. In a small percentage of cases, symptoms may also appear in girls. treatment Patients are very simple and only by avoiding exposure to these hemolysis agents.