Patient's question:
Problem Description: phe=307Doctor's answer:
This is one of the few treatable genetic metabolic diseases. Early diagnosis and treatment should be pursued to avoid irreversible damage to the nervous system. Since symptoms may not appear in children in the early stages, laboratory testing is essential.(1) Newborn Screening
Newborns are fed milk for three days, and their peripheral blood is collected on thick filter paper, dried, and then sent to the screening laboratory. The phenylalanine concentration can be determined semi-quantitatively using the Guthrie bacterial growth inhibition test; alternatively, a colorimetric quantitative determination can be performed under the action of phenylalanine dehydrogenase, which has a lower false-negative rate. When phenylalanine levels exceed 0.24 mmol/L (4 mg/dL), which is twice the normal reference value, retesting or venous blood sampling for quantitative determination of phenylalanine and tyrosine should be conducted. Typically, the plasma phenylalanine level in affected children can be as high as 1.2 mmol/L (20 mg/dL) or higher.
(2) Urine Ferric Chloride Test and 2,4-Dinitrophenylhydrazine Test
Both tests are chemical colorimetric methods for detecting phenylketone in urine. Due to their poor specificity, they may yield false-positive or false-negative results and are generally used as initial screening for older children.
(3) Plasma Free Amino Acid Analysis and Urinary Organic Acid Analysis
Analysis of amino acids and organic acids in plasma and urine not only provides biochemical diagnostic evidence for this disease but also helps differentiate other possible amino acid and organic acid metabolic defects.
(4) Urine Pterin Analysis
High-performance liquid chromatography (HPLC) can be used to measure the levels of neopterin and biopterin in urine, allowing for the differentiation of various types of PKU:
- Children with PAH deficiency exhibit increased total pterin excretion, with a normal neopterin-to-biopterin ratio.
- Children with DHPR deficiency show increased total pterin excretion and decreased tetrahydrobiopterin.
- Children with 6-PTS deficiency present with an elevated neopterin-to-biopterin ratio and increased neopterin excretion.
- Children with GTPCH deficiency exhibit decreased total pterin excretion.
(5) Enzyme Diagnosis
PAH is only present in hepatocytes, making its activity detection challenging. The activities of the other three enzymes can be measured using peripheral blood red and white blood cells or skin fibroblasts.
(6) DNA Analysis
Currently, DNA analysis can be used for genetic diagnosis of PAH and DHPR defects. However, due to the high genetic polymorphism, the results must be interpreted with caution.