Let the rare | start with "screening" to prevent genetic defects

The last day of February each year is the International Day of Rare Diseases. Rare diseases, one of the greatest challenges facing human medicine, are attracting increasing attention.

At present, there are more than 7,000 kinds of rare diseases recognized internationally, about 350 million rare disease patients worldwide, and more than 20 million rare disease patients in the mainland. Like "Moon Child", "Glass Man", "Porcelain Doll", "Butterfly Baby", these fairy tale poetic names correspond to albinism, hemophilia, osteogenesis imperfecta, bullous epidermal laxity; and "do not eat human fireworks", "one of the thousands", is synonymous with phenylketonuria, congenital adrenal hyperplasia.

Most patients with rare diseases, sooner or later, will have multi-organ function involvement, especially respiratory, circulatory and nervous system, which may lead to respiratory failure, liver and kidney function impairment, physical and intellectual backwardness, inability to take care of themselves, and even life-threatening. The earlier the intervention, the better the effect. According to statistics, about 80% of rare diseases are caused by genetic defects, 50% occur at birth or childhood, of which 30% cannot live past 5 years old, and about 35% of neonatal deaths are caused by rare diseases.

Early screening is the most cost-effective means of preventing rare diseases. According to the three-level prevention strategy of birth defects, relevant physical examinations and genetic counseling should be done before pregnancy; prenatal screening and diagnosis should be done during pregnancy; and newborn disease screening and diagnosis should be done after childbirth.

Today, we interviewed Mr. Ji Hongwei, Marketing Director of Maternal and Child Health Product Line, Perkin Elmer Diagnostics Division, with topics related to rare diseases and newborn screening. PerkinElmer is a global technology leader in prenatal screening and newborn screening, and in the 1990s, PerkinElmer began to cooperate with the Chinese health system to introduce products, technologies and experiences in newborn disease screening to China, helping to establish a newborn disease screening system, providing screening tests for 70% of newborns in China every year.

Q

At present, the hospital routinely carries out prenatal screening, newborn screening and other tests, which rare diseases can be screened out?

A

Ji Hongwei: The number of screening diseases carried out in each region varies due to the development of medical technology levels. At present, there are more than 50 kinds of genetic metabolic diseases that can carry out large-scale newborn disease screening in China, of which congenital hypothyroidism and phenylketonuria are compulsory screening diseases of the state, and the screening rate has reached more than 98%. Congenital adrenal hyperplasia, G6PD deficiency, amino acid metabolism disease, organic acid metabolism disease, fatty acid metabolism disease, etc. are regional diseases.

How can rare diseases that are not routinely screened in hospitals be screened? Who needs to have these supplemental tests done further?

Hongwei Ji: Screening for some rare diseases is not yet included in routine hospital screening, such as lysosomal storage disease (i.e., LSD), severe combined immunodeficiency disease (SCID), spinal muscular atrophy (SMA), and adrenoleukodystrophy (X-ALD). With the advancement of technology, these diseases have a corresponding screening, diagnosis, treatment plan, early diagnosis and intervention of them will be able to effectively control the disease. In terms of screening techniques, LSD and X-ALD can be detected by tandem mass spectrometry, and SCID and SMA can be detected by real-time PCR. Perkin Elmer has partnered with some hospitals in The Country to conduct pilot studies on screening programs for these diseases.

In fact, everyone has 5-10 defective genes, once both parents have the same defective genes, it is possible to give birth to a baby with a rare disease, although this probability is very low, but for the family encountered, it is 100%, followed by a lifetime of pain. Therefore, it is recommended that every family can pay attention to newborn disease screening, and also call for more rare disease programs to be included in the scope of routine screening.

What is the significance of newborn screening for the prevention and treatment of rare diseases?

Ji Hongwei: Through newborn screening, some congenital and hereditary diseases that endanger life can be screened in groups at an early stage, and early diagnosis and treatment can be carried out to avoid affecting the growth and development of babies due to brain, liver, kidney and other damage, resulting in growth backwardness, intellectual disability, and even death.

Although some rare diseases have not yet been specifically drugged, early diagnosis and intervention are still very valuable for the treatment of rare diseases, and even completely control the disease. For example, the well-known phenylketonuria, the child is screened out at birth, and then through strict dietary intervention treatment, you can achieve lifelong life and work like a normal person.

Perkin Elmer screened out the first case of phenylketonuria in the 1980s and 1990s, and is now married, has children, and lives a completely normal life. Similarly, there are congenital hypothyroid patients, after early detection (within 2 months) adhere to thyroxine replacement therapy, patients can grow healthily, normal intelligence, if the diagnosis and treatment is too late, may cause different degrees of mental retardation, short stature.

Babies look healthy at birth, but do they still need to be screened for genetic metabolic diseases in newborns?

Ji Hongwei: Most babies with genetic metabolic diseases look normal at birth, but after 3 to 6 months of birth, some abnormal manifestations will gradually appear. If it is diagnosed at this time, the best time for treatment is missed, which will lead to the baby's physical and intellectual development lagging behind and difficult to improve, which will bring a great financial and mental burden to the family.

Perkin Elmer is a technology leader in the field of newborn screening, and what are the main technical means of newborn screening on a global scale?

Ji Hongwei: At present, time-resolved fluorescence immunoassay, direct fluorescence method, tandem mass spectrometry, gas chromatography-mass spectrometry, real-time quantitative fluorescence PCR and genetic testing are mainly used in newborn screening.

PerkinElmer has instruments and technical solutions in these areas. For example, the GSP fully automated immunoassay analyzer based on time-resolved fluorescence immunoassay and direct fluorescence method can realize the detection of the traditional four diseases, including congenital hypothyroidism, phenylketonuria, G6PD and congenital adrenal hyperplasia.

In addition, our NeoBase kit based on tandem mass spectrometry can assist in the clinical detection of more than 40 genetic metabolic diseases at one time, and the LSD kit can assist in the screening of 6 lysosomal diseases at the same time. The SCID plus kit based on real-time PCR can assist in screening for severe combined immunodeficiency disease and spinal muscular atrophy.

In recent years, the application of whole genome sequencing technology in the field of neonatal disease screening has also attracted more and more attention, and gene sequencing technology can provide an additional layer of screening in addition to traditional technical means to detect a large number of rare and otherwise difficult to detect disease genetic markers. We believe that with the continuous advancement of screening and treatment technology and the continuous efforts of all sectors of society, we will be able to bring more tangible help to rare disease patients and their families.

In the face of rare diseases, every family has a lot of powerlessness and hardships, and love and persistence make every rare life have a unique color! On February 28, 2022, the International Rare Disease Day, let us pay more attention to rare diseases, and work together for love "Khan", rare disease patients can also have a colorful life!

Edited by: Yeah Reviewer: Xiao Ran