How to prevent and control the four diseases that are screened for by taking blood samples from the soles of newborns after birth?

This is the 3870th article of Da Yi Xiao Hu

1. Phenylketonuria (PKU)

1. Introduction to PKU

It is an autosomal recessive disease and a common amino acid metabolism defect. It is named because of the enzyme defect in the phenylalanine metabolism pathway of the child, which causes a large amount of metabolites such as phenylpyruvic acid to be excreted in the urine. The main clinical features of this disease are mental retardation, epileptic seizures and hypopigmentation, and the incidence rate varies by race and region.

2. Screening for PKU

Using phenylalanine (Phe) as the screening indicator, detection methods can include fluorescence analysis, quantitative enzyme method, bacterial inhibition method and tandem mass spectrometry.

3. Diagnosis of PKU

3-4 days after breastfeeding, use thick filter paper to collect peripheral blood from the soles of the newborn's feet, dry it, and send it for examination. When the Phe content exceeds 2 times the normal level (＞0.24mmol/L, 4mg/dl), the examination should be repeated or venous blood should be collected for quantitative determination of Phe and tyrosine. If it continues to increase, the diagnosis can be confirmed. The plasma Phe of the child can be as high as 1.2mmol/L (20mg/dl) or more.

4. Treatment of PKU

1. Low phenylalanine diet

① Low-Phe diet treatment should be started immediately after PKU is diagnosed. The younger the age when treatment begins, the better the effect. Low-Phe diet can prevent children from developing mental retardation, reduce epileptic seizures and abnormal behavior, and prevent brain damage.

② Infants can be fed special low-Phe milk powder; when adding complementary foods to young children, low-protein foods such as starch, vegetables and fruits should be the main focus.

③Since Phe is an essential amino acid for protein synthesis, its deficiency can also lead to damage to the nervous system. Therefore, 30-50 mg/(kg•d) should be supplied to maintain the blood Phe concentration at 0.12-0.6 mmol/L.

2. Monitoring of blood phenylalanine concentration

① Dietary treatment should be carefully planned, and Phe levels should be tested regularly during treatment so that the diet can be adjusted.

② For those who are receiving low-Phe diet treatment, if the Phe concentration is abnormal, monitor it once a week; if the blood Phe concentration is within the ideal control range, monitor it 1-2 times a month to maintain the blood Phe concentration within the ideal control range for each age group.

③ Conduct physical development assessments regularly, conduct intellectual development assessments at 1, 3, and 6 years of age, and control diet until at least 10 years of age.

5. Prevention and prognosis of PKU

Couples with a family history of the disease should use DNA analysis or amniotic fluid pterin detection in the early pregnancy to perform prenatal diagnosis of the fetus. Conducting newborn screening to detect PKU children as early as possible, early treatment, and controlling diet, low-Phe diet at least until 10 years old, can prevent the occurrence of mental retardation in most cases.

6. Clinical manifestations of PKU

Children are born normal, usually with the first symptoms appearing at 3-6 months, and becoming obvious at 1 year old. Children who are not discovered early and given timely dietary treatment may have the following three clinical manifestations.

1. Appearance: About 90% of children have lightening of hair, skin and iris due to melanin production disorder a few months after birth. About 1/3 of children have dry skin, often with eczema, which may last for several years.

2. The retardation of the nervous system and intelligence is a prominent manifestation of this disease, which may be accompanied by mental and behavioral abnormalities, such as restlessness, hyperactivity and aggressive behavior. A few patients may present with increased muscle tension and hyperreflexia of the tendons.

3. Other symptoms include vomiting and skin eczema, and urine and sweat have a rat urine odor.

2. Congenital hypothyroidism (CH)

1. Introduction to CH

CH is short for hypothyroidism. It can be divided into two categories according to the cause: sporadic and endemic. Sporadic hypothyroidism is caused by congenital thyroid dysplasia or enzyme deficiency in the thyroid hormone synthesis pathway. Endemic hypothyroidism is mostly caused by iodine deficiency in water, soil and food in the living area.

2. Screening for CH

The indicator is thyroid-stimulating hormone (TSH). Currently, most domestic and foreign methods use dried blood drop paper to detect TSH concentration in newborns 2 to 3 days after birth as an initial screening. The positive cut-off value of TSH concentration depends on the laboratory and the test kit. Generally, it is considered positive if it is greater than 10-20mU/LμIU/ml. When the screening result is greater than the positive cut-off value, serum samples are collected to test T4 and TSH for confirmation.

3. Diagnosis of CH

For those with positive CH screening results, serum T3, T4, and TSH were measured to further clarify the diagnosis.

Normal children's serum T3 is 1.2-4.0nmol/L, T4 is 90-194nmoL/L, and TSH is 2-10mU/L. ① If T4 is reduced and TSH is significantly increased, the diagnosis can be confirmed. ② If blood TSH is increased and FT4 is normal, it is diagnosed as hyperTSHemia. ③ Thyroid ultrasound examination, bone age determination, and thyroid isotope scanning (ECT) can be used as auxiliary means.

4. Treatment of CH

1. Treatment principles

① Regardless of the cause, treatment should be provided immediately once confirmed to avoid or reduce brain damage.

② People with congenital thyroid abnormalities require lifelong treatment.

2. Thyroid hormone replacement therapy

①Children with CH are given levothyroxine (L-T4) for treatment, taken orally once a day.

②The initial therapeutic dose of L-T4 is 6-15 g/kg/d, so that FT4 reaches the normal range within 2 weeks.

③In subsequent follow-up, the L-T4 maintenance dose must be individualized and adjusted according to blood FT4 and TSH concentrations.

④ Blood FT4 should be maintained within the range from the average value to the upper limit of normal.

⑤ For patients with high TSH blood level, L-T4 treatment may be given as appropriate, and the initial treatment dose can be adjusted according to the degree of TSH increase.

3. Regularly review FT4 and TSH concentrations to adjust the L-T4 treatment dose.

①Recheck 2 weeks after the first treatment. If abnormal, adjust the L-T4 dose and recheck 1 month later.

② If thyroid function is normal, recheck once every 2-3 months for children under 1 year old, once every 3-4 months for children between 1 and 3 years old, and once every 6 months for children over 3 years old.

4. Conduct physical development assessments regularly and intellectual development assessments at 1, 3, and 6 years of age.

5. Patients with thyroid dysplasia and ectopic thyroid require lifelong treatment. Other children can reduce medication or stop medication for 1 month after 2-3 years of regular treatment, and recheck thyroid function, thyroid ultrasound or thyroid isotope scan (ECT). If TSH is elevated or accompanied by decreased FT4, L-T4 should be given for lifelong treatment; if thyroid function is normal, it is temporary hypothyroidism, and medication should be stopped and regular follow-up should be performed.

5. Prevention and prognosis of CH

CH can be diagnosed and treated early through neonatal screening, which can reduce brain damage and improve prognosis. If not treated in time, it can lead to intellectual and physical development disorders in children.

6. Clinical manifestations of CH

In the neonatal period, there may be delayed disappearance of jaundice, constipation, and less activity. If not discovered in time, intellectual and motor development disorders may occur, ultimately affecting the child's normal life.

The early or late onset of symptoms and the severity of symptoms in CH children are determined by the secretory function of the residual thyroid cells in the children. Children with congenital thyroid deficiency or enzyme deficiency will develop symptoms 1 to 3 months after birth; those with thyroid dysplasia will usually develop symptoms 3 to 6 months after birth, and occasionally 4 to 5 years old.

3. Erythrocyte glucose-6-phosphate dehydrogenase deficiency (G6PD)

1. Introduction to G6PD

1. This disease is caused by mutations in the gene that regulates G-6-PD. So far, there are more than 122 mutations in the G-6-PD gene. The G-6-PD gene is located at Xq28, with a total length of about 18.5Kb, containing 13 exons, encoding 515 amino acids. G-6-PD deficiency is inherited in an X-linked incomplete dominant manner. Both male hemizygotes and female homozygotes are affected, and G6PD is significantly deficient. Whether female heterozygotes develop the disease depends on the proportion of their G-6-PD-deficient cells in the cell population, which has different degrees of expression in clinical practice, so it is called incomplete dominance.

2. G6PD is a hereditary hemolytic disease that is distributed all over the world. It is estimated that more than 200 million people in the world suffer from G-6-PD deficiency, but the incidence varies greatly among regions and ethnic groups. High-incidence areas include Mediterranean coastal countries, East India, the Philippines, Brazil and Cuba. In my country, this disease is mainly seen in the Yangtze River Basin and provinces to its south, with a higher incidence in Yunnan, Hainan, Guangdong, Guangxi, Fujian, Sichuan, Jiangxi, Guizhou and other provinces (autonomous regions), and it is relatively rare in the northern region.

2. The three commonly used methods for G6PD screening are:

① Methemoglobin reduction experiment;

② Fluorescent spot test;

③ Nitro blue tetrazolium (NBT) paper method.

3. Diagnosis of G6PD

1. This disease should be considered in patients with the following medical history:

① Positive family history or past medical history are helpful for clinical diagnosis.

② The patient has acute hemolytic symptoms and a history of eating broad beans or taking medications.

③Neonatal jaundice, or chronic hemolysis of unknown cause since childhood.

2. In laboratory examinations, the specific direct diagnostic method is the determination of red blood cell G-6-PD activity, and the normal value varies depending on the measurement method.

4. Treatment of G6PD

1. After a clear diagnosis, know the triggering factors and try to avoid them.

2. For patients with acute hemolysis, remove the predisposing factors and assess the degree of hemolysis and anemia. During the hemolysis period, adequate water should be provided, attention should be paid to correcting electrolyte imbalance, and oral sodium bicarbonate should be taken to keep the urine alkaline to prevent hemoglobin deposition in the renal tubules.

3. Patients with mild anemia do not need blood transfusion. After the cause is removed, hemolysis usually stops on its own within 1 week. For patients with severe anemia, red blood cells with normal G-6-PD can be transfused 1 to 2 times.

4. Close attention should be paid to renal function. If renal failure occurs, effective measures should be taken promptly.

5. Neonatal jaundice can be treated with blue light, and in severe cases, exchange transfusion therapy should be considered to prevent the occurrence of bilirubin encephalopathy.

5. Prevention and prognosis of G6PD

In areas with a high incidence of G-6-PD deficiency, a population survey for G-6-PD deficiency should be conducted; people known to be G-6-PD deficient should avoid eating broad beans and their products, avoid taking drugs with oxidizing effects, and strengthen prevention of various infections.

6. Clinical manifestations of G6PD

Newborns may develop jaundice caused by hemolysis. Infection, pathological birth, hypoxia, mothers giving oxidant drugs to breastfeeding newborns, or newborns wearing clothes with the smell of mothballs can all induce hemolysis.

Favism is common in