Over Thanksgiving break, I was talking with one of my cousins about our childhood memories, laughing about the good and the bad. We wound up talking about a period when this cousin was quite sick. I was very young when my cousin was experiencing all of these medical issues, but I shared with them the one memory I had of them being unwell, explaining that I hadn't realized the severity of their situation. They went on to tell me that they had been diagnosed with hereditary spherocytosis (HS) at the age of 5, an inherited blood disorder. Their red blood cells (RBCs) were shaped like a sphere rather than a disk. As a result, RBCs are more fragile than their normal biconcave shaped. Anemia, jaundice, and an enlarged spleen are some of the signs of this condition, all of which my cousin experienced (MedlinePlus Genetics, 2013). Anemia occurs when the spleen works harder to break down and filter RBCS, causing RBCs to be destroyed earlier than usual. There is a defect in the RBCs membrane cytoskeleton. There was a study done to identify the protein causing the defects in HS. It found that deficiency in the spectrin protein was the most common abnormality among the participants of the study however there were a number of other protein defects and over half of the participants showed normal protein levels. However, the study concluded that there was no relationship between hemoglobin levels or splenectomy and protein deficiency (Aylin, 2012). A splenectomy, blood transfusions, cholecystectomy, and phototherapy are all common treatments for HS (Manciu, 2017). My cousin received everything except phototherapy. The abnormal permeability of spherocytes causes an increase in the influx of sodium into the intracellular space, which in turn increases the need for ATP as the activity of the sodium potassium pump rises to counteract the higher intracellular sodium concentration (Zamora, 2022).
HS is often a straightforward clinical diagnosis of a genetic disorder, and parents/patients can get counseling regarding the implications of the diagnosis, the prognosis, and the danger of passing the mutation onto their own children if/when they choose to do so (J Health Popul Nutr., 2010) People with this disorder have a normal life expectancy if properly treated, but there is an increased risk of life-threatening infection and they are more likely to fall sick (Rull, 2018). My cousin also expressed some personal concerns and curiosities, such as how they didn't understand why they had this condition when no one in her immediate family did, and how doctors advised her to join in clinical studies nearby because there wasn't much study done on this disorder. After this conversation I was intrigued to find out more about spherocytosis. According to the US National Library of Medicine, only 5 studies could be discovered, two of which were either terminated or withdrawn research. I also discovered that, while HS is normally inherited in an autosomal dominant fashion, it can also be inherited in an autosomal recessive form. I wanted to shed some light on this disorder because it is a rare condition with little research. Do you think further studies should be done on this disorder?
Citations:
Hereditary spherocytosis: MedlinePlus Genetics [Online]. Hereditary spherocytosis: MedlinePlus Genetics: 2013. https://medlineplus.gov/
J Health Popul Nutr. 2010 Feb; 28(1): 107–109. doi: 10.3329/jhpn.v28i1.4529
Manciu S, Matei E, Trandafir B. Hereditary Spherocytosis - Diagnosis, Surgical Treatment and Outcomes. A Literature Review. Chirurgia (Bucur). 2017 Mar-Apr;112(2):110-116. doi: 10.21614/chirurgia.112.2.110. PMID: 28463670.
Zamora EA, Schaefer CA. Hereditary Spherocytosis. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Aylin Canbolat Ayhan, Inci Yildiz, Sedef Yüzbaşıoğlu, Tiraje Celkan, Hilmi Apak, Alp Ozkan & Serap Karaman (2012) Erythrocyte membrane protein defects in hereditary spherocytosis patients in Turkish population, Hematology, 17:4, 232-236, DOI: 10.1179/1607845412Y.0000000001
Rull DG. Hereditary Spherocytosis | How is HS inherited? [Online]. Hereditary Spherocytosis | How is HS inherited? | Patient: 2018. https://patient.info/
Given that sickle cell provides protection against malaria, would HS (essentially the opposite of sickle cell) lead to increased vulnerability? Additionally, what kind of populations are more at risk for developing this hereditary disorder (disease epidemiology is always so cool)
ReplyDeleteupdate: i found an article that actually shows that HS provides a somewhat protective effect against malaria which is due to to any cell surface abnormality.
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC54739/pdf/pnas01043-0420.pdf