What is phenylketonuria? What tests should be done to determine whether there is phenylketonuria?

There are now irresponsible and informal hospitals that make a variety of diagnoses. Some people clearly do not have phenylketonuria, or the condition is not serious, but in the mouths of these quack doctors, it becomes a fatal disease. Since some people do not understand phenylketonuria and do not know what tests to do for a true diagnosis, today we will explain to you what tests should be done to determine whether you have phenylketonuria?

Phenylketonuria (PKU) is an inherited metabolic disorder that causes an increase in a chemical called phenylalanine in the blood. Phenylalanine is derived from a person's diet and is used by the body to make protein. Phenylalanine is found in all food proteins and some artificial sweeteners. Without dietary treatment, phenylalanine can accumulate in the body to harmful levels, causing mental retardation and other serious problems.

Women who have high levels of phenylalanine during pregnancy are at increased risk of being born with mental retardation, heart problems, a small head (microcephaly), and developmental delays. This is because the baby is exposed to very high levels of phenylalanine in the mother before birth.

PKU occurs in 1 in 10,000 to 1 in 15,000 newborns in the United States. Newborn screening for PKU has been used since the 1960s, but its serious signs and symptoms are rarely detected.

Symptoms of PKU range from mild to severe. Severe PKU is called classic PKU. Babies born with classic PKU appear normal in their first few months of life. However, if not treated with a low-phenylalanine diet, these babies can develop mental retardation and behavioral problems. Other common symptoms of untreated classic PKU include seizures, developmental delays, and autism. Boys and girls with classic PKU may also have skin eczema and lighter skin and hair than family members who do not have PKU.

Babies born with less severe PKU (moderate or mild PKU) are likely to have less severe intellectual developmental delays unless they are treated with a special diet. If a baby has only very mild PKU, often called mild hyperphenylalaninemia, there may be no problem and special dietary treatment may not be needed.

PKU is inherited in families in an autosomal recessive pattern. Autosomal recessive inheritance means that a person has two copies of the altered gene. Usually, each parent of a person with PKU carries one copy of the altered gene. Because each parent has a normal copy of the gene, they do not show signs or symptoms of PKU.

Mutations in the PAH gene cause PKU. Mutations in the PAH gene result in low levels of an enzyme called phenylalanine hydroxylase. These low levels mean that the phenylalanine in a person's diet cannot be metabolized (changed), so it accumulates to toxic levels in the blood and body. Excessive intake of phenylalanine can cause brain damage unless dietary treatment is started.

Examination items: serum phenylalanine, urine analysis, electroencephalogram, CT scan, magnetic resonance imaging, phenylalanine tolerance test

Since children have no symptoms or atypical symptoms in the early stages, laboratory testing is necessary.

1. Neonatal screening

After the newborn is breastfed for 3 days, blood is collected from the heel of the foot, absorbed on thick filter paper, dried and mailed to the screening center. The Guthrie bacterial growth inhibition test is used for semi-quantitative determination. The principle is that phenylalanine can promote the re-growth of the suppressed Bacillus subtilis. The content of phenylalanine in the blood is determined within the range of the growth circle. It can also be quantitatively determined by colorimetry under the action of phenylalanine dehydrogenase, and the false positive rate is low. When the phenylalanine content is >0.24mmol/L (4mg/dl), which is twice the normal reference value, the venous blood should be rechecked or quantitatively determined for phenylalanine and tyrosine. The normal phenylalanine concentration is 0.06-0.18mmol/L (1-3mg/dl), while the plasma phenylalanine of children without the disease can be as high as 1.2mmol/L (20mg/dl) or more, and the tyrosine in the blood is normal or slightly low.

2. Urine ferric chloride test

Used for screening of older infants and children. When ferric chloride is dripped into the urine, if a green reaction occurs immediately, it is positive, indicating that the concentration of phenylalanine in the urine is increased. In addition, the dinitrophenylhydrazine test can also measure phenylalanine in urine, and a yellow precipitate is positive.

3. Plasma amino acid analysis and urine organic acid analysis

It can provide a biochemical diagnostic basis for this disease and can also identify other amino acid and organic acid metabolic diseases.

4. Urine Pterin Analysis

High-pressure liquid chromatography (PHLC) is used to determine the levels of neopterin and biopterin in urine to identify various types of PKU. In children with typical PKU, the total excretion of pterin in urine is increased, and the ratio of neopterin to biopterin is normal. In children with DHPR deficiency, the total excretion of pterin is increased, and tetrahydrobiopterin is reduced. In children with 6-PTS deficiency, the excretion of neopterin is increased, and the ratio of neopterin to biopterin is increased. In children with GTP-CH deficiency, the total excretion of pterin is reduced.

5. Enzyme diagnosis

PAH only exists in hepatocytes and needs to be determined by liver biopsy, so it is not suitable for clinical diagnosis. The activities of the other three enzymes can be measured by peripheral blood red blood cells, white blood cells or skin fibroblasts.

6. DNA analysis

In recent years, the technology has been widely used in PKU diagnosis and prenatal diagnosis of heterozygotes. However, due to the polymorphism of the gene, the analysis results must be cautious.