The International Day of Rare Diseases is coming, and the family dilemma of patients with rare diseases： it is difficult to seek medical treatment and expensive medicine.
Reporter Fu Chang and intern Ren Yawen report that the last day of February every year is "International Day of Rare Diseases". On February 23rd, the Rare Diseases Branch of Guangdong Medical Association held the 2019 "International Rare Diseases Day" charity clinic in Guangzhou Hero Square. Experts said that many patients with rare diseases still face problems such as high drug costs, and the public lacks sufficient understanding of rare diseases, calling on the society to pay more attention.
Parents’ voice of children with rare diseases: it is difficult to seek medical treatment and the medicine cost is expensive.
On the morning of the 23rd, there was a light rain in Guangzhou. Although the weather is not beautiful, there are still crowds in front of the charity clinic booth in Hero Square. Many parents came to consult with their children. They frowned slightly and pulled the doctor to ask various questions, as if they had caught the "life-saving straw". In the crowd, the reporter met Mr. Deng and his 4-year-old daughter Jia Jia (a pseudonym).
Mr. Deng told reporters that it was accidental that Jia Jia was diagnosed with a rare disease. "One day, I found that Jia Jia kept blinking when playing with her mobile phone. We thought she had an eye problem, so we quickly took her to the community hospital to see a doctor." He said that as a result, after repeated examinations, ophthalmologists could do nothing about Jiajia’s illness and could not tell why. Seeing that Jia Jia’s symptoms became more and more obvious, Mr. Deng and his wife asked around and visited experts. After many referrals, in November 2017, Jia Jia was finally diagnosed with mucopolysaccharide storage disease in Guangzhou Women and Children Medical Center.
It is understood that mucopolysaccharidosis (MPS) is a rare disease with congenital metabolic abnormality, with an incidence rate of about one in 100,000. Because of the lack of lysosomal enzymes, patients can’t decompose mucopolysaccharides in the body. The accumulated mucopolysaccharides will affect the normal function of cells and destroy many organs of the body such as brain, heart valve, lung and bone. On May 11, 2018, the National Health and Wellness Committee and other five departments jointly formulated the "First List of Rare Diseases", and mucopolysaccharide storage disease was also included.
Jia Jia, who was diagnosed with this disease, is undoubtedly unfortunate, but compared with other children with mucopolysaccharidosis, Jia Jia may be lucky. Because at the time of diagnosis, Jia Jia’s mother had been pregnant for 30 weeks with her second child, and worried that the second baby would get sick, she immediately went to the hospital for a umbilical cord blood puncture. After confirming the health of the fetus, Jia Jia and her unborn sister were successfully matched, and a bone marrow transplant was successfully performed after her mother gave birth.
"Because of early diagnosis and early treatment, Jia Jia’s current height and intellectual development are normal." Mr. Deng said that in order to help his daughter with treatment, he had previously joined a group of patients with mucopolysaccharide storage disease, many of whom were still struggling on the road of seeking medical treatment and even took many detours. "As far as I know, the average diagnosis time of patients with rare diseases is 7 years, which often misses the ideal treatment period." Mr. Deng said. The reporter also saw at the scene that some children around the age of 10 are only 1 meter tall and have obvious abnormal physical characteristics.
The reporter learned that for the treatment of mucopolysaccharide storage disease, in addition to the bone marrow transplantation surgery accepted by Jia Jia, some experts also proposed gene therapy and enzyme replacement therapy. The former is still in the state of research and development, while the latter refers to the artificial production of enzymes that patients lack and intravenous injection into patients. However, at present, this therapy has not entered the domestic market, and the drug price is expensive, with an annual cost of up to 2 million yuan, which requires lifelong medication. Without the support of medical insurance, ordinary families simply cannot afford it.
Experts appeal: Rare diseases need attention from all walks of life.
It is reported that the World Health Organization (WHO) defines rare diseases as diseases with an incidence of 0.65-1‰, and there are currently about 7,000-8,000 species in the world. "However, due to the large population base in China, rare diseases are not uncommon in terms of the number of patients." Liu Li, chairman of the Rare Diseases Branch of Guangdong Medical Association and chief physician of the Department of Genetics and Endocrinology of Guangzhou Women and Children Medical Center, said. On the occasion of the International Day of Rare Diseases, Liu Li hopes to raise the social attention of rare diseases through public welfare clinics.
She introduced that one of the difficulties in the diagnosis of rare diseases lies in parents’ insufficient understanding of rare diseases. "In real life, a sick child has not been diagnosed and other sick children have been born. This kind of thing often happens." She said that 70%-80% of rare diseases are hereditary diseases, and 70%-80% of rare diseases occur in childhood. Liu Li suggested that parents should have a clear understanding of their children’s development and pay attention to their abnormal conditions in time. If there have been rare cases in the family, prenatal diagnosis must be made before giving birth.
"Rare diseases are rare, doctors who can diagnose rare diseases are even rarer, and drugs that can treat rare diseases are even rarer." This is the true voice of parents of children such as Mr. Deng. Liu Li said that for this reason, the Rare Diseases Branch of Guangdong Medical Association goes to remote places to give academic lectures every year, so that grassroots doctors can understand rare diseases. When patients are found to be abnormal, they can also help to refer them to experts in time, so that patients can seek medical treatment and avoid detours.
She also pointed out that due to the small number of users, high research and development costs, and the lack of relevant laws and regulations in the country, pharmaceutical companies are reluctant to take the initiative to produce rare diseases, which makes it difficult and expensive for patients to buy drugs. However, this situation is gradually improving. With the release of the first batch of rare diseases catalogue in China and the recent joint notice issued by the four departments, the value-added tax policy for rare diseases drugs has been clarified, and the tax rates of some raw materials and imported drugs have been reduced, which will reduce the drug cost of more patients with rare diseases in the future. The patients also called for more drugs to be included in the medical insurance reimbursement.
[Introduction of Several Rare Diseases]
Gaucher’s disease
Gaucher’s disease is a rare monogenic disease and the most common lysosomal storage disease, which is autosomal recessive, with an incidence of about 1/50,000~1/100,000. The mutation of glucocerebrosidase gene (GBA) leads to the lack of glucocerebrosidase activity, which leads to the accumulation of glucocerebrosidase in the lysosomes of macrophages in liver, spleen, bone, lung and even brain, forming a typical storage cell, namely "Gaucher cell", which leads to pathological changes in the affected tissues and organs, and the clinical manifestations are that multiple organs are involved and gradually aggravated. Clinically, Gaucher’s disease can be divided into three types: type ⅰ (non-neuropathy type); Type Ⅱ (acute neuropathy); Type ⅲ (chronic or subacute neuropathy). Caucasians account for about 95% of Gaucher’s disease type I, while Asians account for more than 50% of Gaucher’s disease type II and III.
Patients with Gaucher’s disease are usually characterized by splenomegaly and thrombocytopenia, which are similar to the clinical symptoms of many hematological diseases. Therefore, most patients with Gaucher’s disease will initially go to the hematology department. Hematologists should conduct glucocerebrosidase activity tests to diagnose or rule out Gaucher’s disease after excluding malignant tumors and other diseases.
Gaucher’s disease is an autosomal recessive genetic disease. If the patient’s parents give birth again, the risk of their children getting sick is 25%. For the families and relatives who have given birth to Gaucher’s disease patients, genetic counseling and detection of pathogenic gene carriers should be carried out. Prenatal diagnosis is the most effective way to prevent high-risk families from giving birth to similar children again.
neonatal diabetes
Neonatal diabetes mellitus is a rare special type of diabetes mellitus, which usually refers to persistent and progressive hyperglycemia that occurs within months after birth. The incidence rate is 1/300,000~1/400,000. In the past, the etiology of this type of diabetes was unclear, and it was regarded as an early-onset type of type 1 diabetes for a long time because it needed insulin treatment.
Neonatal diabetes can occur in both men and women, and the onset age ranges from a few days to several weeks. The earliest symptoms that lead to medical treatment are unexplained polyuria and drinking water, often accompanied by feeding difficulties, weight loss or even emaciation, mild to moderate dehydration, mental drowsiness and so on. Some children were diagnosed with elevated blood sugar in routine physical examination, but delayed diagnosis may also lead to symptoms of diabetic ketoacidosis, such as vomiting, shortness of breath, listlessness and even coma. This is a serious manifestation of diabetes, which requires urgent treatment in the hospital. A few children will have motor retardation and occasional convulsions.
Most neonatal diabetes is caused by gene mutation, and the treatment and prognosis of neonatal diabetes caused by different gene mutations are different, so chromosome microarray and gene mutation detection are needed to further clarify the cause diagnosis. Neonatal diabetic children with KCNJⅡ gene and ABCC8 gene mutation can control their blood sugar better by oral sulfonylureas than by exogenous insulin injection.
glycogen storage disease
Glycogen accumulation disease is a kind of glycogen metabolism disorder disease caused by congenital enzyme deficiency, most of which are autosomal recessive inheritance (except for X-linked recessive inheritance of type VI), and its incidence rate is 1/(2 ~ 25 thousand). The process of glycogen synthesis and catabolism requires the participation of various enzymes. There are 12 types of clinical diseases caused by these enzyme defects, among which liver diseases are the main types I, III, IV, VI and VII. Type ⅱ, ⅴ and ⅶ are mainly muscle tissue damage. The common feature of these diseases is glycogen utilization disorder, which increases in liver, muscle, kidney and other tissues.
Glycogen accumulation disease type I is caused by the deficiency of glucose -6- phosphatase system in liver, kidney and other tissues, and it is the most common glycogen accumulation disease, accounting for about 25% of the total. The main manifestations are hypoglycemia, growth retardation, muscle relaxation, abdominal distension, abnormal liver function, metabolic acidosis, increased triglyceride and uric acid in blood tests, and gout and kidney calculi may occur in older children. Most children are prone to infection. Children with the above-mentioned clinical manifestations need to go to a hospital with the conditions for genetic analysis for genetic examination and definite diagnosis and disease classification.
This disease is a rare treatable disease, and diet therapy is the main treatment for glycogen storage disease. The proportions of three nutrients in total calories are: carbohydrate 60-70%, protein 10-15%, and fat < 30%. The carbohydrate is mainly raw corn flour, and raw corn starch releases glucose at a moderate speed in the body, thus maintaining the stability of blood sugar in the body for a period of time, avoiding hypoglycemia and improving metabolic abnormalities in the body. The vast majority of carbohydrates eaten by children in one day must be replaced by raw corn flour. Infant’s diet is fed continuously for 8-10 hours with nasogastric tube at night to maintain blood sugar stability and avoid fasting for more than 4 hours. Pay attention to avoid eating foods containing sucrose, fructose, lactose and galactose, such as fruits, sweets, sugary drinks and commercial products containing milk; In the aspect of fat intake, it is necessary to limit the intake of saturated fatty acids, take more units and polyunsaturated fatty acids. Blood sugar should be maintained between 3.9 and 6.7 mmol/L, so as to ensure the normal growth and development of children.