Sickle Cell Disease

Different Types of Sickle Cell Disease

The following are the most common types of sickle cell disease (SCD)²:

• HbSS: A person with SCD who inherits two sickle cell genes (“S”), one form each parent. This is known as sickle cell anemia and it is considered to be the most severe form of the disease.
• HbSC: A person who inherits one sickle cell gene (“S”) from one parent and another gene for an abnormal hemoglobin called “C” from the other parent. This is generally considered to be a milder form of SCD.
• HbS beta thalassemia: A person who inherits one sickle cell gene (“S”) from one parent and one gene for beta thalassemia from the other parent. Beta thalassemia is another form of anemia that has two types: “0” and “+”. Those with HbS beta 0-thalassemia usually have a severe form of SCD compared to people with HbS beta +-thalassemia, who tend to have a milder form of the disease.
• HbSD, HbSE, and HbSO are all rare types of SCD: People who have these forms of the disease inherit one sickle cell gene (“S”) and one gene from an abnormal type of hemoglobin (“D”, “E”, or “O”). The severity level of these uncommon forms of SCD varies.

How Sickle Cell Disease Affects the Body

Signs of sickle cell disease can present themselves during the first year of life, often starting at 5 months old. Common symptoms include fatigue, lethargy, and jaundice.² People with sickle cell anemia can experience growth delays and they can be prone to having more infections. The most common complication of sickle cell anemia is pain caused by the sickle cells traveling through smaller blood vessels, getting stuck, and clogging the blood flow. This also causes inflammation as oxygen flow becomes reduced.  A sickle cell crisis, an episode of sudden and severe pain, may result in an emergency room visit with hospitalization for treatment. Reduced oxygen flow may also result in damage to the major organs such as the brain, eyes, lungs, liver, heart, spleen and kidneys.¹

Treatment Options

Treatment options vary depending on the type of sickle cell disease and the severity of the patient’s symptoms. Mild forms like HbSC or SCT may not need any treatment, while the most severe form, HbSS (sickle cell anemia), often requires pain management strategies as well as medications to prevent complications. Other forms of treatment include blood transfusions, medication and increased hydration to provide pain relief.

Hydroxyurea and Endari (L-glutamine oral powder) are two medicines approved by The Food and Drug Administration (FDA) for treating SCD. Hydroxyurea is the gold standard of treatment and is used to reduce pain episodes and the need for blood transfusions.³  Endari is generally reserved for those that cannot tolerate hydroxyurea or their pain is not controllable. Endari is an amino acid that plays a key role in protein synthesis.⁴ It is important to know that  both forms of treatment are effective in lowering the incidents of pain crisis but do not cure the disease.

Another treatment, which is the only currently known cure for SCD, is a stem cell transplant (also called a bone marrow transplant). During this procedure, healthy cells, called stem cells, are infused into the body to replace damaged or diseased bone marrow. Bone marrow is the center of the bone where blood cells are made. Bone marrow transplants are being used increasingly to successfully cure SCD. This option does present challenges, however. It requires a matched donor (a person with similar, compatible bone marrow) and can sometimes cause severe side effects, including occasional life-threatening illness or death.⁵

Gene therapy is an exciting new form of treatment that is currently only used in limited clinical trials. The purpose of this treatment is to target the cause of a disease rather than the symptoms. Within this process, the genes are modified to treat the disease.⁶ It is useful for a number of reasons such as replacing or bypassing the role of a missing gene, or to augment therapy for a disease. Although it is not the standard of care for SCD, it’s yielding promising results for some patients as shown in the case of then 27-year-old Jennelle Stephenson.

Stephenson, featured in an episode of CBS’ “60 Minutes”, was born with SCD and participated in a National Institutes of Health (NIH) trial in December 2017 where she received genetic treatment. She was one of a small group of SCD patients who received an infusion containing altered DNA, using her stem cells that had been genetically modified. The new DNA in the genetically-modified cells were used in the hopes of curing her. In the video, she was asked to rate her pain on a scale from one to 10, with 10 being the most severe. In response, she described her frequent pain episodes as, “Beyond a 10... it’s terrible, it’s horrible,” she said. Stephenson described feeling pain everywhere from her “cheek-bones” to her “legs” and she went on to say that her pain episode,“feels like bone-crushing pain”. She struggled with the debilitating pain episodes since childhood and said that she had friends who died from the disease. Stephenson also said that before receiving gene therapy, it was a challenge to perform simple daily tasks such as walking up the stairs or  being able to work or go to school without interruption because these activities would trigger a pain crisis. When asked what she always wanted to do if she did not have the disease, she replied, “I just want to run to be honest... just [do] basic things”.  After completion of the process, nine months later, Stephenson was said to be cured.⁷   

She used to struggle walking up a flight of stairs, but after the treatment she said her body felt “strong” and she was able to do activities such as swimming, running and even taking karate classes, all of which she was never able to do before receiving gene therapy treatment.

Conclusion

As with Jennelle, pain crises from sickle cell disease can significantly alter a person’s quality of life. The increased availability and success of pain management strategies can make daily living more managable, but this doesn’t cure the disease. According to a study published by the CDC in October 2020, the average life expectancy estimates of people with SCD are only 43–54 years.⁸ At this time, the only known cure for SCD is a bone marrow stem cell transplant, which as mentioned above is a difficult procedure that can sometimes cause severe side effects, including occasional life-threatening illness or death.⁷ The clinical trial conducted at NIH has shown positive results using gene therapy as another option in “curing” SCD.  

With advances in medical testing and clinical trials using gene therapy, the definitive cure for SCD patients is promising. SCD patients may have been uninsurable in the past, but new advances in treatment could change this if life expectancy rises once treated.  We have seen advances in other diseases recently with Hepatitis C, a disease that also made it difficult to obtain life insurance coverage for individuals. These improvements in Sickle Cell Disease should lead to people living longer and healthier lives. With improved longevity, we can see a day in the future where life insurers would open up to accepting more individuals with Sickle Cell Disease for life coverage.