Xiaoxu's Story - Can "Normal People" Not Suffer from Rare Diseases?

35-year-old Xiao Xu (pseudonym) is usually healthy and has a normal work and life. However, during a physical examination, multiple abnormalities were found in the liver function test indicators. But Xiaoxu usually does not have any upper abdominal discomfort, skin itching, nausea, vomiting or other discomfort. After careful consideration, Xiaoxu came to Zhongshan Hospital for treatment. Further examination results made him uneasy: liver pathology revealed partial liver cell edema and steatosis (20%) with inflammatory cell infiltration in the puncture tissue.

After multidisciplinary consultations, Xiaoxu underwent whole genome sequencing(WGS). Combined with clinical manifestations, ultimately he was diagnosed with a rare disease - Familial Intrahepatic Cholestasis (FIC).

Familial intrahepatic cholestasis is a rare, autosomal recessive inherited disease. It is due to genetic mutations that lead to impaired bile secretion in the liver, resulting in intrahepatic cholestasis and ultimately leading to liver failure and death. The disease can recur or continue to progress, and cannot be cured. The prognosis is related to classification and early intervention. Patients with individual subtypes of the disease progress rapidly after onset, often dying from liver failure from infancy to adolescence. The disease also includes developmental abnormalities, mental disorders, and short stature.

The preliminary analysis results of Xiaoxu's WGS did not reveal any clear pathogenic or suspected pathogenic variants. However, through further genetic analysis and literature review, it was found that both the FIC related genes TJP2 and ATP8B1 have a "Variable of unknown clinical significance (VUS)" mutation. Combined with clinical phenotype, it suggests that Xiaoxu belongs to the mild type of benign recurrent intrahepatic cholestasis. However, even in mild cases, if not intervened in a timely manner, some patients may experience recurrent episodes and progress to chronic persistent liver disease, ultimately leading to severe progressive FIC and even sensorineural hearing loss. Only early detection and intervention can improve prognosis. Luckily, Xiaoxu discovered the disease in early stages, conducts whole genome sequencing, received a clear diagnosis, and early intervention and targeted treatment were conducted in a timely manner, so the prognosis was greatly improved.

After a clear diagnosis, Xiaoxu also conducted further family verification on his family, and the results showed that the mutation site on ATPBB1 was inherited from his father. It was found that his brother and daughter also carried the mutation site separately; The mutation site on TJP2 comes from Xiaoxu's mother. Both his brother and daughter have a certain probability of giving birth to sick offspring.

Therefore, the Health Management Center of Zhongshan Hospital has customized a personalized health management plan for Xiao Xu and his family, including routine monitoring of bile stasis, liver disease, nutrition, and routine audiogram examinations, and requires him to avoid using potential ototoxic and inducing drugs; At the same time, relevant disease risk assessments and health management recommendations were provided for high-risk relatives carrying pathogenic mutations, and genetic counseling was conducted.

Unlocking the Life Code and Escorting a Healthy Journey

The whole genome is the sum of all genetic material, including all biogenetic information of over 20000 genes and over 3 billion base pairs. Whole Genome Sequencing (WGS) is the detection of all genetic material in the human body. At present, whole genome sequencing has been widely applied in the auxiliary diagnosis and treatment of various diseases, and expert consensus has been formed in the field of genetic disease detection.

The Health Management Center (Sheshan Campus) of Zhongshan Hospital affiliated with Fudan University is established in the picturesque Sheshan Scenic Area of Songjiang, Shanghai. With the strong medical, educational, and research capabilities of Zhongshan Hospital, it promotes "high-quality health management" and creates a health management center that integrates prevention, screening, disease prediction, diagnosis, treatment, and rehabilitation. The hospital provides one-stop, intelligent, and full lifecycle health management services that cover the entire process of health management, including customized personalized plans, establishment of personal health records, proactive follow-up by professional teams, precise appointment and referral, and improvement of health literacy.

Dunwill Medical, in collaboration with Zhongshan Hospital affiliated to Fudan University develops whole genome sequencing with the aim of "unlocking the code of life and escorting a healthy journey". The main services include screening for disease related gene carriers, screening for genetic tumors, screening for genetic cardiovascular diseases, personalized medication guidance, and disease multi gene risk assessment; Being able to provide diagnostic evidence for difficult to diagnose and treat diseases, as well as professional report interpretation services, has important significance for driving precise treatment of patients.

Target audience:

Would-be couples, couples concerned about genetic risks

People with a history of tumors, cardiovascular and cerebrovascular diseases, genetic diseases, and other related diseases

People with adverse drug reactions or a family history of adverse drug reactions

Individuals with a family history of hereditary diseases, such as hereditary tumors, hereditary cardiovascular diseases, etc.

Sample type: Peripheral blood 6ml

Report period: 30 working days