HbS/β+ thalassemia: Really a mild disease? A National survey from the AIEOP Sickle Cell Disease Study Group with genotype‐phenotype correlation

Abstract

Objectives HbS/β+ patients’ presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/β+ patients, with genotype‐phenotype correlation, in order to offer guidance for clinical management of such patients. Methods Retrospective cohort study of HbS/β+ patients among 15 AIEOP Centres. Results A total of 41 molecularly confirmed S/β+ patients were enrolled (1‐55 years, median 10.9) and classified on β+ mutation: IVS‐I‐110, IVS‐I‐6, promoter, and “others.” Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS‐I‐110 group presented the lowest median age at first SCD‐related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS‐I‐6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers. Conclusions HbS/β+ is not always a mild disease. Patients with IVS‐I‐110 mutation could benefit from a standard of care like SS and S/β° patients. Standardization of treatment is needed.

A case of Sβ+ sickle cell disease diagnosed in adulthood following acute stroke: it’s 2021, are we there yet?

“…By contrast, Sβ+ and SC are rarer genotypes and usually initially present with less severe anemia and infrequent vaso-occlusive crises in childhood. Over time, patients with these subtypes often gradually develop multiple complications such as stroke, avascular necrosis of bones requiring joint replacement, sickle cell retinopathy, and hepatosplenic sequestration [6][7][8]. Due to their gradual clinical progression, these rarer subtypes may be misunderstood and remain undiagnosed for years, such as in this case.…”

“…Ischemic stroke is a well-established complication of SCD, with a recent study suggesting an incidence rate of approximately 2% in children and young adults [10]. While the existing literature suggests that the overall risk of stroke is lower among Sβ+ patients, it still represents a significant source of morbidity [6][7][8]. This is evident in the patient described in this report, who continues to have gait problems and imbalance, expressive aphasia, and cognitive impairment requiring her mother to oversee her overall care.…”

Difficulties in the diagnosis of HbS/beta thalassemia: Really a mild disease?

“…In the study by Notarangelo et al [12] , HbS/β patients with confirmed molecular accuracy were classified according to the β mutation, and it was reported that some mutation differences with IVS-I-5 (G>C), IVS-I-5 (G>A) and IVS-I-110 had a more severe phenotype and clinical presentation, and some mutation differences were associated with a milder phenotype [8] . The study by Belisário et al [22] reported that the newly discovered 92 (C>T) and IVS-II-844 (C>A)/IVS-II-839 (T>C) mutation presented as a very mild HbS/β+ case.…”

“…It may cause serious and life-threatening complications [13] [14] . Patients who were admitted to a hospital with complaints of stroke and sequestration were reported [12] [27] . Sequestration crisis is seen in HbSS or HbSβ 0 cases before the age of 5, while, in HbS/β cases, it may delay until puberty and early adulthood and progress rapidly, resulting in death as a result of hypovolemic shock [12] .…”

“…On the other hand, there are limited data to describe the profile of clinical complications of HbS/β patients [8] . The clinical phenotype severity varies even among individuals with the same genotype [12] . The complication incidence varies over time in the same individuals and among different individuals [4] [11] .…”