Screening for genetic metabolic diseases

Screening for genetic metabolic diseases is essentially a type of pre-disease prevention and control method for newborns and high-risk groups. The core value is to diagnose patients before they develop irreversible organ damage and intellectual disability. More than 90% of the diseases that can be intervened, as long as they are diagnosed and treated early, patients can achieve a quality of life and life expectancy that is almost the same as that of the general population.

Last year, when I was following up at the genetics clinic, I met a little girl in third grade with braids. When she entered the door, she was handed a certificate for the third prize in a mathematics competition. She is a patient with phenylketonuria who was diagnosed with phenylketonuria by taking heel blood test when she was 3 days old. She has been drinking special formula powder and controlling her natural protein intake since she was one month old. Now she pays more attention to her diet than other children, and she has not fallen behind in running, jumping and studying. If she had not been screened, there was a high chance that she would suffer from mental retardation and convulsions after six months of age, and she would not even survive to school age.

It is often said in the industry that "screening is more important than diagnosis" because this type of disease is too hidden - to put it bluntly, the "switch" of a certain metabolic pathway in the body is broken, and the toxins that should be decomposed are piled up in the body, damaging the brain and liver, and the nutrients that should be synthesized cannot be produced and hinder development. Nowadays, the national free newborn screening package generally covers 4-7 high-incidence and interventionable diseases, such as phenylketonuria and congenital hypothyroidism just mentioned. Localities adjust slightly according to the incidence. The time requirement for collecting heel blood is 72 hours after birth and after adequate breastfeeding. We are afraid that there is not enough food and metabolism has not started, and a false negative is a waste of time.

The most controversial issue now is whether to add money for expanded screening in addition to free screening. The packages on the market range from dozens to hundreds, and the prices range from hundreds to thousands. Dr. Zhang from the community maternal and child health care hospital I know often advises ordinary families not to blindly follow the trend: "The incidence rate of many diseases is only one in 100,000 or 200,000. Most of them are found to have no mature intervention methods. Parents cry for half a month with the abnormality report. The final re-examination is a false positive, which is not a mistake." This is indeed not nonsense. The more items are expanded for screening, the higher the false positive rate. I have seen too many parents receive a re-examination call so that they can't sleep all night. In the end, after two or three re-examinations, they were all false alarms, which wasted their emotions.

But a 1-year-old child I received last month left me speechless. The child looked normal until he was half a year old, but then he suddenly couldn't sit up and didn't respond to his name. It took more than three months of tests before he was diagnosed with methylmalonic acidemia. If he had spent more than 100 yuan more for basic expanded screening at birth, the diagnosis could have been made at that time, and he could be controlled by taking special milk powder and vitamin B12 supplements. Now the brain damage is irreversible, and subsequent rehabilitation can only allow him to return to a semi-autonomous life, which is really a pity.

My general advice to parents is never "must be screened" or "screening is not necessary." If you have a child who died of unknown causes at home, your parents are close relatives, or you have given birth to a child with a metabolic disease before, you are a high-risk group, let alone expand screening. Relevant carrier testing should be done before delivery; if there are no high-risk factors at all, then weigh and consider whether you can accept the one in ten thousand chance of getting the disease. If you can, just do it for free. If not, just spend hundreds more to buy it for peace of mind. There is no need to be led away by anxious articles from marketing accounts.

There is another direction that has been discussed a lot recently: Should the coverage of screening for genetic metabolic diseases be extended to adults? Those who support it believe that many late-onset metabolic diseases are often misdiagnosed as epilepsy, liver disease, and neurodegenerative diseases, and early screening can avoid many detours; those who oppose it believe that the incidence rate in adults is lower and that large-scale screening is a waste of medical resources. Not long ago, there was a 28-year-old patient who suffered from recurrent liver damage for unknown reasons. After two years of examination, he was finally diagnosed with hepatolenticular degeneration after a metabolic screening. After two months of copper excretion treatment, his indicators became normal. If he had been diagnosed a few years earlier, he would not have suffered so much.

In fact, if you work in this industry for a long time, you will find that there is never a perfect screening plan. All choices are essentially a balance between probability and affordability. After all, for a single family, if the probability of one in 10,000 falling on their own head is 100%, the sky will fall. What we can do is to put all the facts, pros and cons on the table, so that everyone can choose the option they don't regret.