What is sickle cell disease?
Sickle cell disease is an inherited blood disorder. Normal red blood cells are smooth and flexible discs, like the letter O, enabling them to move easily through your child’s blood vessels. In contrast, sickle cells are stiff, sticky and often shaped like the letter C. Sickle cells tend to cluster together and to the lining of blood vessels, making it difficult for them to move through small blood vessels. These clusters can create blockages in your child’s small blood vessels, stopping the movement of healthy, oxygen-carrying blood. This blockage decreases oxygen delivery to the tissues which can cause pain and organ dysfunction and is what causes the majority of the complications of the disease.
脾脏有助于从血液中过滤细菌感染并充当旧红细胞的回收中心，它倾向于比正常的红细胞更快地破坏畸形的镰状细胞。镰状细胞仅活约14天，而正常的红细胞可以活到120天。这导致慢性缺乏血液中的含氧红细胞，称为贫血. Sickle cells can also damage your child’s spleen, increasing the risk of certain potentially life-threatening bacterial infections.
Millions worldwide suffer complications from sickle cell disease and nearly 300,000 infants with sickle cell disease are born each year. Approximately two million African-Americans, or 1 in 12, are "carriers" of the sickle mutation (called sickle cell trait). About 100,000 people in the United States have sickle cell disease. It mostly affects children of African descent, Hispanics and Caribbean ancestry, but also is found in those with Middle Eastern, Indian, Latin American, and Mediterranean heritage. The Global Health Initiative at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center is working to improve survival for children with sickle cell disease around the world, including programs to establish newborn screening for sickle cell disease and developing research partnerships in Liberia and Haiti.
什么是不同类型的镰状细胞疾病？
All children with sickle cell disease have inherited sickle cell trait (HbAS) from at least one parent. People with sickle cell trait have one copy of the HbS gene and one copy of the normal hemoglobin A gene (HbA). Sickle cell trait is not a form of sickle cell disease, although in rare circumstances, sickle cell trait can become symptomatic. People with sickle cell trait may pass on the HbS gene to their children.
There are several different types of sickle cell disease that differ in symptoms and severity. The type of sickle cell disease depends on the specific gene variant that your child has inherited.
镰状细胞贫血（HBSS）
- The child has two copies of the HbS gene, one inherited from each parent.
- This is the most common and most severe form of sickle cell disease.
- 镰状细胞疾病的多种症状和并发症发生。
- Severe, chronic anemia is present.
Sickle cell with hemoglobin C disease (HbSC)
- The child has one HbS gene and one defective hemoglobin C gene (HbC).
- A more mild to moderate anemia is typical.
- All complications of sickle cell disease may occur but tend to be a milder degree.
Hemoglobin S-β-thalassemia
- 这有两种形式：HBSβ0和HBβ+ thalassya。
- The child has one HbS gene and one β thalassemia gene.
- The degree of anemia is varied depending on the specific genetic type.
- Children may experience a broad range of sickle cell symptoms and disease severity. HbSβ0 thalassemia is very similar to HbSS. Hbβ+ thalassemia severity is varied but usually mild.
Other forms of sickle cell disease (compound heterozygotes), including HbSE, HbSO, and HbSD
- The child has one HbS gene and another abnormal hemoglobin gene.
- Symptoms vary depending on the specific genetic defect.
How we care for sickle cell disease
Dana-Farber/Boston Children's Cancer and Blood Disorders Center is an international leader in improvingtreatment和受镰状细胞疾病影响的儿童的生活质量。我们治疗镰状细胞贫血（HBSS），具有血红蛋白C疾病（HBSC），血红蛋白S-beta- thalassya（HBSβ0和HBβ0和HBβ+Thalassemia）以及包括HBSD，HBSO，HBSO和HBSE在内的较少常见的复合形式。
Through ourSickle Cell Disease Program，患有镰状细胞疾病的儿童可以进入世界著名的儿科血液学家，最高的护理护理以及包括羟基脲和干细胞移植在内的最新治疗选择。我们也是全国为数不多的使用一种称为PreciseType的技术的中心之一，可以将献血者与需要输血的镰状细胞患者相匹配。精确的型使我们的医生可以更精确地输入患者的血型，并降低患有输血供体血液的抗体的风险。
Gene therapy for sickle cell
Thesickle cell gene therapy clinical trialfocuses on newborn hemoglobin. Newborns have a different hemoglobin called fetal hemoglobin that doesn't sickle. The goal of this clinical trial is to flip the switch in SCD red cells back to fetal hemoglobin to prevent sickling from occurring.
Dana Farber/波士顿儿童研究人员发现，称为BCL11A的基因表达的变化会影响胎儿血红蛋白的水平，并花了几年的时间设计一种防止BCL11A产生的方法，从而导致临床试验。治疗过程类似于干细胞移植。去除患者的血液干细胞，然后进行数月的基因修饰，以降低BCL11A的表达并诱导健康的胎儿血红蛋白的产生。然后通过静脉输注将基因修饰的细胞退还给患者，以使产生镰状的成年血红蛋白沉默。
学习莫re about theGene Therapy Program.
Sickle Cell Disease |症状和原因
What are the symptoms of sickle cell disease?
镰状细胞疾病症状的严重程度可能取决于特定的遗传类型，甚至在同一类型的遗传类型中。每个孩子的症状可能不同，症状可能很难预测。镰状疾病的症状和并发症可能包括以下内容。
贫血
贫血is the most common feature of all the sickle cell diseases. Anemia may delay normal growth and development and decrease energy and endurance.
疼痛危机（也称为血管熟悉的危机）
This occurs when the flow of blood is blocked to an area because the sickle-shaped cells have become stuck in the blood vessel. Pain can occur anywhere but most often occurs in the bones of the arms, legs, chest, and spine. Painful swelling of the small bones of the hands and feet (dactylitis) can occur in infants and toddlers. Priapism results from sickling that occurs in the penis. This results in a painful and unwanted erection. Any interruption in blood flow to the body can result in pain, swelling, dysfunction, and possible death of the surrounding tissue not receiving adequate blood and oxygen.
Acute chest syndrome (ACS)
This occurs when sickle-shaped cells stick together and block the flow of oxygen in the vessels in the lungs. It can be life-threatening and is the leading cause of death in children and adults with sickle cell disease. ACS can be triggered by asthma crisis, infection (viral or bacterial), or pain (particularly in the chest) and can progress rapidly to respiratory failure.It resembles pneumonia and includes fever and breathing symptoms such as cough or difficulty catching breath. ACS often occurs suddenly, when the body is under stress from infection, fever, or dehydration, and multiple episodes can cause permanent lung damage.
Bacterial infection and sepsis
In most children with sickle cell disease, by toddlerhood, the spleen becomes scarred and permanently damaged and no longer has full function. The spleen is important in the body’s defense against serious bacterial infections; therefore, children with sickle cell disease are at risk for life-threatening bacterial infections. Fever (>38.5⁰C or 101.5⁰F) is a symptom that must be evaluated immediately to rule out a life-threatening bacterial infection.
Splenic sequestration (pooling)
镰状细胞会阻塞脾脏的血液出口，从而导致脾脏中镰状细胞聚集，从而导致贫血突然恶化。由于被困的血容量的增加，脾脏变得扩大和痛苦。如果不及时治疗，可能会威胁生命。严重的隔离发作需要手术去除脾脏。
Stroke
这是镰状细胞疾病的儿童突然而严重的并发症。镰状细胞可以阻止为大脑提供氧气的主要血管。血液和氧气流向大脑的流动会导致大脑造成毁灭性的损害。A的症状中风可以包括软弱，尤其是在身体的一侧；言语不清;发作;混乱;头晕或协调丧失；或严重的头痛。一只中风后，一个孩子更有可能患有更多中风，并且需要预防性治疗，并需要慢性重复输血。
Jaundice
Jaundiceis a common sign and symptom of sickle cell disease. Sickle red blood cells are destroyed prematurely in the spleen. The recycling of sickle hemoglobin from these cells produces increased levels of the yellow bilirubin protein that discolors the skin and eyes. Chronic high bilirubin levels can lead to gallstone formation.
Other
Any and all major organs are also affected by sickle cell disease. The liver, heart, kidneys, gallbladder, eyes, bones, and joints can suffer damage from the abnormal function of the sickle cells and their inability to flow through the small blood vessels correctly. Problems may include:
- leg ulcers
- bone/joint damage
- kidney damage and loss of body water in the urine
- eye and retinal damage
是什么导致镰状细胞疾病？
The following are the most common ways a child can develop sickle cell disease:
- If both parents have sickle cell trait, each of their children will have a 25 percent chance of having sickle cell disease.
- If one parent has sickle cell disease and the other has sickle cell trait, each of their children will have a 50 percent chance of having sickle cell disease and a 50 percent chance of having sickle cell trait.
- If one parent has sickle cell disease and the other does not, all of their children will have sickle cell trait, but none of them will have sickle cell disease.
Sickle Cell Disease |Diagnosis & Treatments
如何诊断镰状细胞疾病？
The first step in treating your child is providing an accurate and complete diagnosis. Early diagnosis of sickle cell disease is essential in providing proper preventative treatment for some of the devastating potential complications. Sickle cell disease can be identified by the following tests:
- review of newborn screening results
- hemoglobin electrophoresis
- complete family history
- additional blood tests
In addition, using genetic testing, we are able to identify the specific type of sickle cell disease as well as your child’s unique genetic variations.
Newborn screening
Certain newborn screening tests are done within the first few days of life on every baby born in the U.S. to detect serious, life-threatening diseases. A hemoglobin electrophoresis is a newborn screening blood test that can determine if your child is a carrier of sickle cell trait or has sickle cell disease.
镰状细胞疾病的治疗选择是什么？
大多数治疗方法旨在缓解症状或预防并发症。
Prevention of bacterial infections and sepsis
大多数患有镰状细胞疾病的儿童必须：
- 服用预防性给药青霉素至少5岁
- complete all routine childhood vaccinations and additional sickle cell specific vaccinations
- maintain vigilance regarding fevers and signs of infection
羟基脲therapy
羟基脲是一种口服药物，可导致人体产生胎儿血红蛋白（HBF），这是一种通常仅在胎儿和非常小的孩子中发现的血红蛋白。Increasing the healthy fetal hemoglobin can significantly reduce the side effects and complications of sickle cell disease.
Transfusion therapy
Blood transfusions可以敏锐地给予严重贫血，急性胸部综合征和其他威胁生命的并发症。患有镰状细胞疾病的儿童可能会接受慢性输血，以防止并发症，例如中风.<
铁螯合物
Sickle cell anemia patients who require chronic red blood cell transfusions to prevent a stroke gradually become iron overloaded. Without removal of this iron, it can build up and become toxic to several vital organs. Iron can be removed from the body by medications called chelators. Children may take chelators orally or by injection in order to remove excess iron from the body. Your child's physician may also recommend specific treatments based on the symptoms your child experiences.
For anemia
预防：
- 叶酸
- hydroxyurea
治疗:
- blood transfusion
For pain
预防：
- drinking plenty of water daily (8 to 10 glasses)
- avoiding dehydration
- 羟基脲药物以防止疼痛事件
治疗:
- receiving fluids intravenously
- 疼痛的药物如非甾体anti-inflamatories (e.g. ketrolac, ibuprofen) and opioids (e.g. morphine, oxycodone)
急性胸部综合征（ACS）
预防：
- 羟基脲
- 激励肺活量测定法（深呼吸）
治疗:
- broad spectrum antibiotics
- blood transfusions to dilute HbS with normal hemoglobin
For splenic sequestrations
- blood transfusions to dilute HbS with normal hemoglobin and promote ‘release' of blood trapped in the spleen
- penicillin for those who have their spleen surgically removed
For stroke
- blood transfusion
Stem cell transplant
Right now, the only cure for sickle cell disease isstem cell transplant (also called bone marrow transplant)– the transplantation of normal blood stem cells from another person (the ”donor”) to your child. In sickle cell disease, the best transplant outcomes are almost always when the donor is a healthy sibling with compatible stem cells. The stem cells replace the sickle blood stem cells and restore normal blood production in children with sickle cell disease.
The first step is to determine if the patient has a compatible full-sibling donor. This is done with a blood test or a swab of the cheek.