Disease screening results are different from tandem mass spectrometry results

Differences in disease screening and tandem mass spectrometry results are a very common clinical situation. In most cases, it is not that one party's detection is "wrong", but is caused by the completely different technical positioning, detection principles, and applicable scenarios of the two. The final diagnosis must not be determined based on one result alone, but must be comprehensively judged based on clinical indications and retest results.

When I was rotating at the Department of Genetics and Metabolism at the Maternity and Child Health Hospital two years ago, I met a couple who came overnight with their 7-day-old baby. The baby's foot blood was collected three days later for a routine newborn disease screening. The preliminary screening for phenylketonuria (PKU) showed positive. The two cried at home for half the night. After searching on Baidu all night, they said that this disease will cause the child to have mental retardation and that the child will have to eat special milk powder for the rest of his life. We retested the tandem mass spectrometry test for the child on the same day, and waited 4 hours for the results. The phenylalanine concentration was only 1.2 mg/dl, which was completely within the normal range. When we asked, we found out that the child had only had two breasts when the blood was collected for the first time, and the feeding period was less than 48 hours. The fluorescence immunoassay used for the primary screening was easily affected by the feeding time, so it directly gave a false positive. The couple's legs were weak when they walked with the child, saying that the past few days had been like a roller coaster.

This situation is really not rare. I checked the statistics of our department last year and found that among the samples that were positive in the initial screening of newborn genetic diseases, almost 7% were negative in the final tandem mass spectrometry re-test. Conversely, there were less than 2% of cases where the initial screening was negative but abnormalities were detected by mass spectrometry. Essentially, the underlying logic of the two types of detection technology is completely different. Most of the general screening projects that you come into contact with on a daily basis, whether it is the primary screening of newborn genetic diseases, the screening of common tumor markers, or even some items in urine routine, all use rapid screening technology, either immune combination color development or dry chemical reaction. To put it bluntly, it is "casting a wide net" and giving priority to ensuring If suspicious samples are not missed, the specificity will naturally be lower. As long as the molecular structure is somewhat similar to the target, or the sample has interference such as hemolysis or lipemia, false positives may occur. Even the sensitivity of some rapid screens is not high. Abnormalities with lower concentrations cannot be detected, and the diagnosis may be missed.

The detection logic of tandem mass spectrometry (also known as LC-MS/MS in the laboratory) is completely different. It is equivalent to first classifying various substances in the blood according to molecular size, and then breaking each type of molecule into pieces to see the unique fragment structure, let alone analogues with similar structures. , even isotopes that differ by an atomic weight can be clearly distinguished. As long as the pre-processing operation is normal, the specificity is almost 100%, and it can simultaneously qualitatively and quantitatively quantify dozens or hundreds of substances at a time. It can accurately identify many rare metabolites that cannot be screened quickly.

There are actually different opinions on the positioning of these two technologies in the industry. Many colleagues in the public health field believe that rapid screening should be used in the general screening stage. It is low-cost and can produce results quickly. Primary health centers can do it. Even if there are false positives, at least high-risk groups can be screened out first and then sent to higher-level hospitals with mass spectrometry conditions for re-examination. The overall cost-effectiveness is the best and suitable for large-scale promotion. Otherwise, the per capita testing cost will be more than ten times higher, and many remote areas cannot afford it, which will lead to more missed diagnoses. However, many clinicians support moving mass spectrometry forward. For example, our hospital now directly adds mass spectrometry options to newborn screening. For an extra cost of more than 200 yuan, 48 genetic and metabolic diseases can be screened at one time, with a false positive rate of less than 0.1%. Parents do not have to wait half a month for the first-month screening results like before. If they are positive, they will go to the hospital for a reexamination. This saves them a lot of trouble and avoids a lot of unnecessary anxiety. Both of these statements are actually valid. No one is right or wrong. It is nothing more than finding a balance between health economic benefits and user experience.

Last year, there was a male patient in his 40s who tested positive for alpha-fetoprotein (AFP) rapid screening at work and was suspected of liver cancer. He came to our hospital and had an abdominal CT with no problems, and a tandem mass spectrometry for quantitative AFP. The indicators were completely normal. Finally, we traced the cause and found out that he had a party with friends the night before the physical examination, drank almost a kilogram of liquor, and stayed up all night. The rapid screening reagent was interfered by alcohol and stress and gave a false positive. Switching to mass spectrometry was completely unaffected by these factors.

Let me tell you, if you encounter a situation where the two results are different, don’t panic, don’t just search online and make a random diagnosis for yourself, let alone question the previous testing agency for fraud or errors. Rapid screening has the value of rapid screening, but mass spectrometry is not a panacea. For example, when some patients with metabolic diseases are in remission, the concentration of metabolites is already close to the critical value, and even the mass spectrometry may fluctuate. At this time, you should also look at whether you have relevant symptoms, family history, and other test results. If necessary, retest, and the reasons for most differences can be found.

To put it bluntly, all test results are auxiliary tools for doctors to refer to, and are never a final verdict. If you really have questions, it is much more useful to find a reliable doctor to interpret it than to speculate on your own.