Disease screening tandem mass spectrometry positive

More than 90% of the positive results in the initial screening are false positives, which does not mean that the subject really has a genetic metabolic disease, so there is no need to be overly anxious at the first time.

Last month, when I was attending a consultation in the Department of Genetics and Metabolism of the Maternal and Child Health Hospital, I met a post-95s mother. She rushed into the clinic with a wrinkled screening report and burst into tears. She said that the heel blood taken 3 days after the baby was born showed high propionylcarnitine and suspected methylmalonic acidemia. She searched for posts from fellow patients all night and was already comparing special milk powder formulas from different brands.

Don't underestimate the sensitivity of tandem mass spectrometry. This thing can capture the concentration of trace metabolites in the blood at the nmol level. A little external interference can easily drift beyond the critical value. For example, if a newborn is born prematurely, is slightly hypoxic at birth, does not send blood for examination in time for two or three days after blood collection, is fed high-energy formula milk just before blood collection, or even has physiological jaundice and takes anti-jaundice drugs at that time, the concentration of certain metabolites may temporarily exceed the standard. I have also encountered something even more outrageous. In the summer, the samples were stagnant at the courier point of the community hospital for three full days before being sent to the laboratory. Half of the test indicators were red, and the parents were notified that there would be no problems after re-collection.

There is another piece of trivia that many people don’t know: the critical values (also known as “cut-off values” in the industry) are different in different laboratories and are determined based on the baseline data of the local population. Don’t compare your child’s results with the values posted by netizens on the Internet. A difference of 0.2 or 0.3 is nothing at all. I have seen many parents stay up all night for three or four nights with results that are 0.3 higher than the cut-off value. It is completely unnecessary.

As for what to do next after a positive test is detected, there is currently no completely unified standard in the industry. One group of experts believes that there is no need to spend extra money. They first resample the sample and do a secondary tandem mass spectrometry test. If the reexamination is still abnormal, then do a urine gas chromatography mass spectrometry test. These two steps can basically eliminate 99% of false positives. The total cost is only a few hundred yuan. The only disadvantage is that parents have to wait for more than a week for the results. The other school of thought is that it is better to do it all in one step. If a positive initial screening test is performed, genetic screening for common inherited metabolic diseases can be directly added. Now the cost of one-generation sequencing has dropped to just over a thousand, and the results can be obtained in 3 days, which saves parents from worrying about it and is actually more friendly to families with reasonable financial conditions. There is nothing wrong with either of these plans. The core depends on the family's acceptance. No one is right or wrong.

As for the mother who came in crying before, we asked around and found out that the baby was born 3 weeks prematurely, with a birth weight of only 4 and a half pounds, liver function was not fully developed, and the speed of metabolizing propionylcarnitine is slower than that of full-term babies. We asked her to go home and feed her normally, and then restarted her feeding after 10 days. The results showed that all indicators were within the normal range. A few days ago, she came to give us a birthday cake for our baby. The little guy was sweating while chasing the ball, and there was no problem at all.

Of course, this does not mean that all positive cases are false alarms. Our department also encounters more than a dozen cases of really positive cases every year, such as phenylketonuria and methylmalonic acidemia. As long as early detection and early intervention are performed, the prognosis is very good, and it will basically not affect intelligence and growth and development. Parents are afraid that they will not take it seriously and think that the baby looks fine and will not go back for re-examination. If they delay intervention until symptoms such as developmental delay and convulsions appear, they will miss the golden intervention period.

To put it bluntly, tandem mass spectrometry screening itself is a preliminary screening tool that "casts a wide net". A positive result is only a reminder that you need further investigation, not a confirmation notification. If you do encounter it, go to the genetic counseling clinic of a regular hospital and ask for clarification. Don't frighten yourself by searching blindly, and don't take it seriously. That's enough.