Fewer than 500 cases were reported globally
Written by | Yan Xiaoliu
Boy or girl?
In the face of Xuan Xuan, who was ambiguous about the external genitalia, the professional doctor could not blurt out the answer.
As soon as Xuan Xuan was born, he was found to have an abnormal appearance of his external genitalia. More than 1 year old, he was diagnosed with Denys-Drash syndrome (hereinafter referred to as DDS). The disease got its name in 1967, and two doctors, Denys and Drash, first described it as a case of a child with kidney disease, gender dysplasia, and nephroblastoma.
This is a rare congenital disease, associated with mutations in the WT1 gene, with fewer than 500 cases reported worldwide.
It causes gender blur in the vulva of the child. "Just looking at the external genitalia, you can't tell the gender. Men and women are a bit alike, but not all. Qin Daorui, attending physician of the Department of Pediatric Urology at Sichuan Provincial People's Hospital, told the "medical community."
The disease is also accompanied by hormone-resistant nephrotic syndrome and kidney tumors. Children often do not live to adulthood and die of severe infection and end-stage renal failure. In their limited childhood, they will be criticized and discriminated against because of gender ambiguity. Going to public toilets is a problem.
Xuan Xuan is a lucky man, with a pair of parents who love him and insist on "doing everything possible to save him".
In less than two years, he has undergone surgeries such as external genital surgery, left renal resection, and left kidney transplantation.
Recently, Xuanxuan, who is more than 2 years old, was discharged from the Sichuan Provincial People's Hospital. Qin Daorui told the "medical community" that he would also have to undergo surgery in the future: remove the stent tube in the transplanted kidney, remove the diseased kidney on the right side, and complete the second stage of urethral repair.
A paper published in 2012 showed that patients with DDS no longer develop the disease after kidney transplantation and have a good long-term prognosis.
"Previously, we had another child with DDS who was in a similar condition to Xuan xuan. But the child didn't wait for a kidney transplant. Qin Daorui said that telling Xuanxuan's story is to popularize the knowledge of rare disease diagnosis and treatment, and the other is to cause the academic community to think and discuss the timing of surgery." This can benefit more children. ”
The image comes from Sichuan Provincial People's Hospital
Male or female?
Xuan Xuan received a definitive diagnosis and did not take too many detours.
At the beginning of his life, he was diagnosed with "hypospadias" due to abnormal appearance of his genitals. "If you look at it from a male perspective, his hypospadias are heavier, and the appearance of the external genitalia is more feminine." Qin Daorui said.
Shortly thereafter, parents listened to the recommendation of patients and began to pay attention to the website "Chicken Amelie" created by the Department of Pediatric Urology of Sichuan Provincial People's Hospital.
This is the first public welfare website in China to focus on congenital hypospadias, founded in 2010. Doctors publish diagnosis and treatment information and answer patients' questions on the website on a daily basis.
Some parents in different places can complete the examination at their place of residence, submit the test results online, conduct online diagnosis, and make an appointment for surgery. When it is time to do surgery, come back to The Sichuan Provincial People's Hospital for hospitalization and treatment.
After 11 years of operation and word of mouth among parents, the pediatric urology department of the hospital has gradually developed into one of the main medical groups in China with the largest number of patients with hypospadias. In 2019, the department admitted a 6-month-old child with severe hypospadias, who was later diagnosed with Frasier syndrome, with fewer than 100 reported worldwide. "Some rare diseases are not uncommon here." Qin Daorui said.
After turning 1 year old, Xuan Xuan followed his parents to the Sichuan Provincial People's Hospital. The family met Mao Yu, deputy chief physician of the Department of Pediatric Urology. He is particularly good at gender development disorders and external genital malformations.
Consultation, physical examination, hormone examination, analysis and verification of the prenatal diagnosis center... After waiting for 1 month in torment, Xuan Xuan was diagnosed with DDS.
Mao Yu explained in detail the characteristics and prognosis of this disease, and also admitted that if you choose treatment, there are too many uncertainties in the process.
Even if the external genital abnormalities are solved, Xuan Xuan still faces risks such as nephrotic syndrome and kidney tumors. According to the literature, when patients with DDS develop nephrotic syndrome, hormone and immunosuppressant therapy is ineffective, the disease often progresses rapidly, and children mostly enter end-stage renal failure before the age of three or four years. If you do not have a kidney transplant, you may die before the age of 6.
Qin Daorui pointed out that because it is a rare disease, there is no guideline or expert consensus on DDS at home and abroad, and the diagnosis and treatment protocols that can be referred to are very limited. "In the very beginning, we are based on the needs of the caregivers to solve the most pressing problems. Then see the tricks. ”
Mao Yu convened the hospital's rare disease MDT team to discuss xuanxuan's situation many times. Based on past experience and experience, the team decided to make a gender decision before Xuanxuan's kidney lesions appeared, and then perform external genital surgery.
The "Chinese Expert Diagnosis and Treatment Consensus on Gender Dysplasia" points out that gender decisions need to take into account disease diagnosis, gonad type and function, risk of gonadal carcinogenesis, external genital morphology, sexual and reproductive potential, psychological sex and status, parents' views and socio-cultural environment.
Early gender determination can prevent the great suffering caused by gender anxiety and gender conflict that may arise in the future, and better integrate into society. It can also reduce the psychological and physical trauma of children and their families.
"It's a complicated thing." Qin Daorui introduced that depending on the external genital conditions of the child itself, surgery is easier to make male external genitalia or female.
Through the scale, assess the child's own sexual psychology. In case the wrong choice is made, the child may grow up with sexual anxiety. It is also necessary to consider the subjective opinions of parents as guardians, as well as the gender of social support of children in the past, that is, whether to be raised as boys or girls.
Pediatric Urology, Pediatric Nephrology, Endocrinology, Organ Transplant Center, Anesthesiology Department, Prenatal Diagnosis Center, Department of Psychosomatic Medicine, Department of Medical Ethics... The MDT team members repeatedly argued and discussed with Xuanxuan's parents, and finally decided to choose the male gender as Xuanxuan's future parenting gender.
This is followed by external genital surgery: robotic-assisted excision of the dysplasiad uterus and vagina, gonadal exploration, and virilization of the external genitalia.
During the operation, the doctor found that Xuanxuan's bilateral dysplastic testicles contained gonadblastoma. This may be related to mutations in the WT1 gene. As a result, bilateral orchectomy was performed at the same time. This means that surgery can achieve urination function, but it cannot preserve fertility function.
The expected kidney tumor came too early
Six months after the operation, Xuan Xuan re-examined the ultrasound of the urinary system and found that nephroblastoma appeared in his left kidney.
Some literature says that children with DDS have a "nephroblastoma disease constitution". Due to the deletion of proteins caused by mutations in the WT1 gene, the associated incidence will increase significantly.
"We foresaw this, but didn't expect it to come so quickly. The cumulative experience of DDS diagnosis and treatment in the world is not much, and it is difficult to accurately predict the development of the disease. From our observations, Xuan Xuan's kidney lesions appeared earlier. Qin Daorui said.
Parents still choose not to give up and do their best to heal.
After joint discussion by the MDT team, the Pediatric Urology Department decided to first remove Xuan Xuan's left diseased kidney and enter the pediatric hematology department for chemotherapy after the operation. At the same time, the MDT team put kidney transplantation on the agenda and laid out the preparation for kidney transplantation related matches in advance.
In November this year, Xuan Xuan was 2 years old and 4 months old, and his right kidney called the police. Urinalysis shows abnormal protein in the urine, blood biochemical tests show a decrease in albumin, nephrotic syndrome is considered.
Several lesions that may occur in DDS are manifested in Xuan Xuan's body.
Further examination revealed that Xuan Xuan's right kidney leaked a large amount of proteinuria every day, and his kidney function was seriously impaired. Protein leakage causes the child's normal physiological needs of plasma albumin to be unsustainable, relying on a large amount of foreign input albumin to maintain, and without effective conservative treatment, the child cannot survive for a long time. At the same time, the right kidney is at high risk of developing new tumors at any time.
According to the current situation of kidney transplantation in Children in China and its reflections on future development, kidney transplantation is the best treatment plan for children with end-stage renal disease. Compared with dialysis, kidney transplantation can not only improve the long-term survival rate of children, but also bring good growth and development and close to the quality of life of healthy children.
Yang Hongji, director of the Organ Transplant Center of Sichuan Provincial People's Hospital, and others discussed the surgical plan three times with the Department of Pediatric Urology. Considering that Xuan Xuan is less than 3 years old, in order to ensure the safety of his life, he decided to perform a kidney transplant while retaining the kidney on his right side.
On December 1, Xuan Xuan waited until the kidney source to complete the transplant operation. Shortly after the operation, he gradually resumed eating, and the transplanted kidney survived well.
"Previously, we had a child with DDS, who was similar to Xuan Xuan's condition. Just after being informed that the kidney match was successful, he died of an infection. This suggests that stubborn urinary protein abnormalities suggest that end-stage renal disease is unavoidable and that transplantation needs to be considered early. This may be the valuable experience that Xuan Xuan brings us. Qin Daorui said.
Tang Yunmin, director of the Department of Pediatric Surgery of Sichuan Provincial People's Hospital, introduced that the state has vigorously supported the diagnosis and treatment of rare diseases in recent years, and the hospital has also taken corresponding measures, one of which is to establish a multidisciplinary joint diagnosis and treatment center for rare diseases (MDT for rare diseases). Xuanxuan has conducted many MDT diagnosis and treatment, each time accurately discussing different prominent problems and tailoring the diagnosis and treatment plan. The success of its diagnosis and treatment is the result of the rapid development of multidisciplinary disciplines and close cooperation in large general hospitals, and is a good example of intimate combat between the patient, the hospital and the doctor. It is hoped that in the future, through further efforts on the MDT platform for rare diseases, more rare diseases will no longer be difficult to diagnose and treat, and more valuable lives can be obtained.
Source:
1. A case of Denys-Drash syndrome. Chinese Pediatric Emergency Medicine. 2012,19(1):107-108. DOI:10.3760/cma.j.issn.1673-4912.2012.01.046
2. Expert diagnosis and treatment consensus on gender development abnormalities in China. Chinese Journal of Pediatric Surgery. 2019,40(4):289-297. DOI:10.3760/cma.j.issn.0253-3006.2019.04.001
3.The current situation of kidney transplantation in children in China and its reflections on future development. Chinese Journal of Organ Transplantation. 2020,41(01):1-2. DOI:10.3760/cma.j.issn.0254-1785.2020.01.001
Source: Medical community
Editor-in-charge: Tian Dongliang
Proofreader: Zang Hengjia
Plate making: Xue Jiao