At the multidisciplinary consultation center of Peking University Hospital, a meeting is held every Friday afternoon. The experts participating in the consultation are basically deputy chief physicians or above. They gather here to provide comprehensive diagnosis and treatment for patients with rare diseases.

  The World Health Organization defines rare diseases as diseases that affect 0.65‰-1‰ of the total population. This is equivalent to tossing a coin more than ten times and getting tails every time.

  According to relevant data, there are more than 7,000 rare diseases in the world, and only 5%-10% of known rare diseases have effective treatment drugs or treatment plans.

There are approximately 20 million rare disease patients in my country, with more than 200,000 new patients every year.

But in fact, they seem to be an "invisible group" in society. According to the "2020 China Rare Disease Comprehensive Social Survey" organized by the China Rare Disease Alliance, the results of a survey of 20,804 diagnosed rare disease patients showed that Chinese rare disease patients have experienced an average of 4.26 years. 42% of the patients had experienced misdiagnosis, and the diagnosis locations were concentrated in big cities such as Beijing, Shanghai, and Guangzhou.

  There are few doctors, it is difficult to diagnose, and there are few and expensive drugs. This seems to be a curse that is difficult to break for patients with rare diseases.

In 2019, Peking University Hospital established a rare disease center and opened a green channel to try to find the fastest way to diagnose and treat rare disease patients through multidisciplinary consultation.

Former Vice President Ding Jie also campaigned for rare diseases as a member of the National Committee of the Chinese People's Political Consultative Conference.

"This is destined to be a problem that will take many generations to slowly solve."

Rare disease "hunters"

  Zhang Chao (pseudonym), a patient who lives in Qingdao, still remembers that it took two years for his father to be diagnosed with ATTR (hereditary transthyretin amyloidosis).

From vitreous opacity to muscle atrophy and the inability to eat anything, my father lost 40 pounds in six months.

  Cancer was the biggest possibility doctors could think of.

Zhang Chao took his father to more than a dozen hospitals in Qingdao, Beijing, and Shanghai for gastroscopy, colonoscopy, and acupuncture.

Finally, ATTR was detected at Shanghai Ruijin Hospital.

This is a familial genetic disease, and 4 of the 5 brothers and sisters of the father's generation were diagnosed one after another.

  Zhang Chao also inherited this disease. In 2019, he saw a post by Yuan Yun, director of the Department of Neurology at Peking University Hospital, recruiting patients for the clinical trial of the new drug clofenac (Vivanxin), so he went there.

  Yuan Yun has been paying attention to this rare disease for 24 years. In 2013, he handed over the main research task of this disease to his student Meng Lingchao.

Under normal circumstances, the liver produces TTR, a protein that is used to transport thyroxine and vitamin A. After the gene mutation, it becomes unstable and is deposited along the blood to various organs: deposited in the limbs, causing numbness and weakness in the hands and feet, and in the eyes Blindness may occur, and heart failure may occur in the heart.

  This disease is similar to a broken "feather duster" - the fixed stick in the middle no longer exists, and the feathers fly everywhere, polluting the environment wherever they go.

  This is a very tricky and difficult disease for doctors to deal with.

One of the gold standards for diagnosis of this disease is the discovery of amyloid fibril deposition in tissue biopsy. Since the deposition of amyloid fibrils in tissues is uneven, if the tissue biopsy happens to obtain tissue without amyloid fibril deposition, a correct diagnosis will be made. brings huge challenges.

  In addition, for a long time, neurologists have believed that this disease must have a family history. If only one person in the family has the disease, it is not this disease.

During Meng Lingchao's diagnosis and treatment, he found that his patients' onset time ranged from 20 to 85 years old, and about half of the patients had no family genetic history.

Therefore, for an elderly patient with no family genetic history, it is easy to be misdiagnosed as other diseases.

  In 2020, new drugs entered China, and doctors subsequently learned to pay more attention to this disease and made more diagnoses.

Meng Lingchao diagnosed two or three cases a year in the past, but now he sees more than 20 cases a year.

  According to data from the Coude Rare Disease Center, there are nearly 300 patients in the existing ATTR community in China, and Zhang Chao is also in this group.

Among them, the detection rate of transthyretin amyloid cardiomyopathy (ATTR-CM) in my country is less than 1%, and most patients' cardiac complaints are misdiagnosed as common diseases such as coronary heart disease.

  The high difficulty and small number of patients have also resulted in very few doctors paying attention to this disease.

Meng Lingchao remembers that at most 30 doctors attended ATTR’s national seminar, while thousands of doctors could easily be invited to common cerebrovascular disease conferences.

"Rare disease doctors are rarer than rare disease patients." Meng Lingchao said.

  In addition to being difficult to diagnose, treatment is even more complicated.

This disease generally causes damage to multiple systems of the human body.

In the cases Meng Lingchao encountered, in addition to peripheral neuropathy such as numbness and weakness in the hands and feet, the patients were also accompanied by various conditions such as cardiac insufficiency and impaired vision.

  "Most rare diseases involve multiple departments. If there is no multidisciplinary consultation, patients need to be treated in several departments at the same time." Yuan Yun introduced that after the establishment of the Rare Disease Center of Peking University Hospital in 2019, as the director of the Rare Disease Center, he has been Begin to promote the establishment of a multidisciplinary consultation system.

  They arrange offline multidisciplinary consultations for rare diseases every Friday afternoon. In July last year, the hospital established an online multidisciplinary consultation platform. Yuan Yun feels that the efficiency of diagnosis and treatment has improved a lot.

Last year, more than 30,000 people were treated for rare diseases in the outpatient clinic of Peking University Hospital. They came from all over the country. 70% of the patients hospitalized in the Neurology Department of Peking University Hospital had rare diseases. Most patients were able to complete the examination and provide preliminary diagnosis within 2-3 days. Diagnosis and treatment plan.

  His father did not wait for the new medicine. Zhang Chao's uncle was treated with Vivanxin at Peking University Hospital for a year, and after spending more than 300,000 yuan, he could no longer afford to stop taking the medicine.

  Fortunately, in September 2020, China's National Medical Products Administration approved Vivanxin for use in ATTR-CM, and some cities also included it in the scope of relevant medical insurance reimbursement.

Under Qingdao's medical insurance reimbursement policy, Uncle Zhang Chao's medication expenses are 20% of the previous price.

  The curative effect of Weiwanxin only targets the heart. Zhang Chao and his patients are still actively writing letters to pharmaceutical companies and medical insurance, health and other departments, hoping that more effective specific drugs will be introduced into China.

A battle without "weapons"

  Ding Jie, 66, has been working on rare diseases for nearly 40 years.

In a retrospective study, Ding Jie and colleagues looked for cases of Alport syndrome (also known as hereditary progressive kidney disease) over the past 30 years and found that the longest diagnosis time was 33 years.

During these 33 years, not only did the patient not receive a correct diagnosis, but he was treated with hormones and immunosuppressants, which are treatments with great side effects and no effect on the patient.

  The end point of this disease is uremia. Without intervention, patients will develop uremia in their 20s to 30s.

However, if drug treatment is intervened early, the patient will develop uremia more than ten years later than those without drug treatment.

  Ding Jie has a family member of a patient. When his eldest son suffered from kidney failure, he donated a kidney to his child, but the cause of the kidney failure was not identified at the time.

When my younger son became ill, he was diagnosed with Alport syndrome at Peking University Hospital. This is the same disease as his older son, but his father no longer had a kidney to donate.

Ding Jie still remembers the father lying on the table in the consulting room crying loudly.

  In 1997, Ding Jie's team used skin biopsy to analyze abnormal type IV collagen caused by mutations, improving the diagnostic rate.

This method is less invasive and less expensive than kidney biopsy, more child-friendly, requires a low technical threshold for diagnosis, and can also be used by local hospitals.

  When she first returned to China in 1995, Ding Jie searched through cases from the previous decade and found only two patients with Alport syndrome detected through kidney biopsy.

In the 20 years since she found a method for skin biopsy, her research team has treated more than 1,000 patients.

  But there is still no cure.

In the face of disease, doctors are like participating in a battle without "weapons".

Ding Jie feels that in this case, "the doctor is not treating the rare disease, but the person." She believes in the saying circulating in the medical community: Occasionally cures, often helps, and always comforts.

  Inherited kidney disease often occurs in childhood. Parents may hide it from their children at first. When the children grow up, they know about it and are unwilling to go to school or eat.

  When a parent asked Ding Jie for help, she found the child and asked him to look into her eyes.

"Son, in fact, it's not just you who has a disease, but my aunt also has a problem. I have poor eyesight. We have to accept that no one is perfect."

  She told him from the child's perspective: You can jump to physical education class like other children, as long as it's not too strenuous.

Proper exercise can help your kidneys work for several more years.

"We adults feel that we can exempt our children from physical education, but it is also important for children to play with friends at school and not to let children feel that they are very different from others."

  Cai Yuanhang (pseudonym) found Ding Jie in 2008.

The year before, his 5-year-old son was diagnosed with Alport syndrome, and then in Ding Jie's case, his lover and eldest daughter were also diagnosed with the same disease.

  This disease has a characteristic that men develop the disease earlier than women and the condition is more severe.

A doctor previously told Cai Yuanhang that this was an incurable disease and that his son would not live to be 13 years old. Cai Yuanhang cried in fear after hearing this.

At Ding Jie's place, Cai Yuanhang gradually learned about the principles of this disease and how to use drugs to slow down the rate of renal failure.

  Drugs are a double-edged sword. Cai Yuanhang's son had already reached the stage of kidney failure when he was 20 years old and in his senior year of high school.

He discussed with Ding Jie and adjusted the dosage of medicine so that the child could pass the college entrance examination smoothly.

Finally, my son was admitted to university and majored in pharmaceutical preparation.

My son reached the stage of uremia in the first half of his freshman year. Fortunately, he waited in line for a kidney source and underwent a kidney transplant in time.

  While Cai Yuanhang was busy with his son's illness, he and Ding Jie were planning to establish the China Alport Syndrome Parents Association.

  In 2012, Ding Jila came to sponsor and held the first parents’ association.

This year, more than 100 families participated, which was all the patients she could find.

By 2023, there will be 3,000 families in the Alport Syndrome Parents Association.

  As the head of the Parents Association, Cai Yuanhang followed Ding Jie to Europe four times to attend international seminars on Alport syndrome in the past 12 years.

He still remembers going to Oxford University in 2014.

It was his first time going abroad, and he had to go through the special channels for his passport and visa.

  He wrote a full page about his problems, including how to view the shortcomings of sick children and how to plan jobs and marriages for them.

He didn't understand English, so Ding Jie asked her daughter to translate for him.

He asked these questions to the families of patients abroad and found that parents all over the world have the same worries about their children.

  After Cai Yuanhang's daughter got married in 2022, she found prenatal diagnosis done by Ding Jie.

Very fortunately, this is a healthy child.

The safe birth of his grandson made Cai Yuanhang feel that his biggest wish in life had come true.

  With the patient organization, Ding Jie feels that her pressure has been reduced: patients are no longer so panicked when they seek medical treatment, and the environment in the clinic is not so depressing.

A “marathon” of relays between generations

  When Ding Jie first came into contact with Alport syndrome, she just treated it as a difficult and complicated disease.

In 2008, Ding Jie was elected as a member of the National Committee of the Chinese People's Political Consultative Conference. From then on, she began to really pay attention to "rare diseases".

At that time, there was no concept and definition of “rare disease” in China.

  Because there is no way to count the number of patients and incidence rates of rare diseases, Ding Jie and other experts discussed with the leaders of the National Health Commission to define rare diseases in a list.

They include in the list rare diseases that have been identified abroad and have relevant drug support, as well as domestic patients and experts.

  In May 2018, five departments including the National Health Commission jointly formulated the "First Catalog of Rare Diseases", and Alport syndrome was also listed among these 121 rare diseases.

"This is a milestone. From this beginning, my country's rare disease group has come to the eyes of more people." Ding Jie said.

  In October of the same year, with the approval of the National Health Commission, the China Rare Disease Alliance was established in Beijing.

Academician Zhao Yupei serves as the chairman of the China Rare Disease Alliance, and Li Linkang, former inspector of the Medical Administration Bureau of the National Health Commission, serves as the executive chairman.

  Rare disease diagnosis and treatment is a systematic project, and the alliance is a bridge linking governments, medical and scientific research institutions, patient organizations, and pharmaceutical companies.

Since its establishment, the alliance has done a lot of work in promoting rare disease diagnosis and treatment capabilities and drug accessibility, and protecting the health rights and interests of rare disease patients, in order to make medicines available and affordable for patients with rare diseases.

  In February 2019, the National Health Commission selected 324 hospitals with strong rare disease diagnosis and treatment capabilities to form a national rare disease diagnosis and treatment collaboration network to provide relatively centralized diagnosis and treatment and two-way referrals for rare disease patients, giving full play to the radiating and leading role of high-quality medical resources.

Among them, Peking University Hospital is the leading hospital in Beijing.

  While treating patients, the Rare Disease Center of Peking University Hospital receives a large number of trainees from all over the country every year.

Yuan Yun has counted that there are already thousands of students studying in neurology alone.

They come from Shenzhen, Henan, Sichuan and other places. After "graduating" from here, they returned to their own hospitals to establish rare disease centers.

The most recent establishment is the Kaifeng Rare Disease Center. At the end of December last year, Yuan Yun was invited to Kaifeng to attend the opening ceremony. They also learned the operating model of multidisciplinary consultation.

  "We have also established a green channel for rare diseases with local hospitals. Patients who are unsure can be transferred to Peking University Hospital for diagnosis. We provide treatment plans and allow patients to return to their hometown for treatment." Yuan Yun said that after multi-hospital cooperation, Beijing Medical University has also avoided A run on resources.

  In 2021, the National Medical Insurance Administration conducted a "soul negotiation" and through multiple rounds of negotiations, the price of drugs for treating SMA (spinal muscular atrophy) was reduced from nearly 700,000 yuan per injection to more than 30,000 yuan, and was finally included in the medical insurance catalog.

Li Linkang shed tears when he heard the news of entering the medical insurance. He knew that this was life-saving good news for patients and their families.

  In February last year, a professor from the Neurology Department of Jiangsu Provincial People's Hospital told Li Linkang that an obstetrician and gynecologist at a Jiangsu hospital discovered something was wrong shortly after the child was born, and immediately contacted a genetic test, which revealed that the child was SMA.

The child takes the medicine on the 19th day after birth, which means that the child's future quality of life can be greatly improved.

"Although rare diseases are difficult to diagnose and treat and poor drug accessibility is still a problem in the world, everyone is working hard to move forward."

  Beijing News reporter Guo Yimeng