Disease screening tandem mass spectrometry positive

Positive tandem mass spectrometry disease screening = confirmed disease. Currently, tandem mass spectrometry, the most commonly used primary screening for neonatal genetic and metabolic diseases in China, has a positive predictive value of only 3%-5% - that is to say, among 100 positive results, at most 5 are cases that truly require clinical intervention, and more than 95% of the remaining are false positives. The risk can be completely eliminated by completing the re-examination process.

Last week, I just met a mother who had just given birth in the genetic counseling clinic. She rushed in with her tightly wrapped baby in her arms. The screening report on her mobile phone was wrinkled by her fingertips. She cried as soon as she sat down. She said that she had checked the information all night and felt that the baby must have an incurable metabolic disease. I took the report and glanced at it. Only propionylcarnitine was slightly higher than the critical value of 0.1. After asking, I found out that the baby's breast milk was not enough in the two days before birth, and he had not eaten much. When the heel blood was collected, he was hungry for most of the day. I asked her to go back to normal feeding for a week and then come back for a review. Yesterday she sent me a message saying that the review results were all normal, and her heart that had been hanging for half a month finally fell back into her stomach.

There are too many factors that can affect the results of tandem mass spectrometry. To put it bluntly, this technology performs a "collective scan" of small molecule metabolites such as amino acids, fatty acids, and organic acids in the blood. As long as a certain value exceeds the preset threshold, a positive report will be reported. However, the metabolic level itself is floating. Take newborn screening as an example. Premature birth, low birth weight, insufficient feeding after birth, crying and lack of oxygen during blood collection, and even the mother having gestational diabetes during pregnancy and taking certain special drugs may cause certain indicators to temporarily rise and cause false positives.

What can I say, the industry has been arguing about the setting of this threshold for almost ten years. One group is the "anxiety reduction group". They feel that the current threshold is too strict and the false positive rate is too high. Many parents cry until they can't breathe while holding the report, and they suffer psychological guilt for half a month for nothing. There are even families who are having conflicts because of this. They just raise the threshold a little, and fewer positives will be screened out, so everyone can worry less. But the other "safety school" firmly disagrees - you have to know that the vast majority of the dozens of genetic metabolic diseases screened by tandem mass spectrometry are preventable and curable but the damage is irreversible. Take phenylketonuria as an example. If the screen is missed, it will be too late when the child shows mental retardation at half a year old. ； But if the baby is caught in the initial screening and starts taking special formula powder from the full moon, the baby can go to school and take college entrance exams like normal children. Missing a diagnosis will ruin a child's life, so it is better to screen for a few more false positives than to let go of a true case. Both sides are reasonable, but there is still no unified standard answer. The screening thresholds in different regions will be fine-tuned based on local incidence rates.

I have come across the most anxious parents. They read the positive report on the hospital's official account at 3 a.m. and drove more than 300 kilometers overnight to the provincial capital. They even prepared a quilt for their baby on the way. The reexamination turned out to be normal. The couple cried with joy at the door of the clinic, holding the baby in their arms, saying that the drive was so hard that their feet were weak. It's really unnecessary. Don't search for extreme cases online as soon as you get the positive report. What you find will be the most serious cases, which will scare you to death. Just go directly to the institution where you are screened. Generally, the local maternal and child health hospital has a special genetic counseling clinic. The doctor will first ask about the feeding and birth conditions of the baby, and eliminate obvious interfering factors. Most of them will ask you to take a blood re-examination for a re-examination. If there are still abnormalities in the re-examination, further urine gas chromatography mass spectrometry and genetic testing will be done to confirm the diagnosis.

Of course, this does not mean that all positive cases are false alarms. Don’t panic if you are really diagnosed. I followed up a child with methylmalonic acidemia last year. After the initial screening, he was positive and then re-examined and was diagnosed. He is a vitamin B12 active type. He started taking B12 regularly from the full moon and controlled his diet a little. He is now in the second grade. The last time he came for the re-examination, he brought me a picture she drew. He scored 98 points in the math test, which is better than many normal children. By the way, when it comes to diagnosis, there are also differences in the industry. Some genetic testing institutions will make a diagnosis as long as they find a heterozygous mutation at a disease-causing site. This makes many parents think that their children have an incurable disease. In fact, this is not the case at all. Many people are carriers of the disease-causing mutation throughout their lives. None of them will get sick. Our clinicians now pay more attention to whether the metabolic indicators are persistently abnormal and whether the baby has corresponding clinical symptoms. The genetic results are only an auxiliary and cannot be a "death sentence" just by relying on a genetic report. This is also the point where clinical and testing institutions have the most quarrels.

After all, the technology of tandem mass spectrometry itself is really good. Twenty years ago, many genetic metabolic diseases could not be detected at all, and by the time they were discovered, they had already caused irreversible damage. Although a positive test may look scary now, to put it bluntly, it is just to remind you and make you pay more attention. Most of the time, it is a false alarm. If the problem is really detected, early intervention can be done. It is not a bad thing by any means. Don't feel like the sky is falling as soon as you see a positive result, just follow the procedure, it's not a big deal.