Gender-Related Differences in Sickle Cell Disease in a Pediatric Cohort: A Single-Center Retrospective Study

Abstract

Sickle cell disease (SCD) is one of the most common monogenic disease worldwide. The incidence of SCD is not strictly gender-related as it is transmitted as an autosomal recessive disorder. In particular, the gender-related differences in pediatric SCD are not well-characterized. To address this matter, we retrospectively analyzed the clinical records of 39 pediatric patients with a diagnosis of SCD (hemoglobin SS genotype) focusing on gender differences analyzing various aspects of the disease and comprising both acute symptoms and late complications. We found various gender-related differences in our pediatric population. In particular, pain crisis frequency per year was significantly increased in the male population with a mean number of crisis per year of 1.6 vs. 0.6 in the female population (p = 0.04). Also, severe complications (both infectious and cardiovascular) were mostly found in the male population. SCD-related late cardiac complications were observed mainly in the male population (p = 0.04). Our data support the hypothesis that gender could play a role in determining the clinical course of SCD, even though further studies are needed to assess the exact weight of its influence over the course of the disease. The higher morbidity in males is a well-known feature of SCD in adults and these findings have been only partially studied in the pediatric population. These differences have, in adults, been attributed to hormonal variations found in the two sexes after puberty. In a pediatric population, other factors must be responsible for these discrepancies. These findings suggest that gender could be a valuable factor in the risk stratification of these patients at diagnosis, and possibly guide therapeutic decisions, with the final aim of personalizing the therapy.

Relationships among genomic ancestry, clinical manifestations, socioeconomic status, and skin color of people with sickle cell disease in the State of Pará, Amazonia, Brazil

“…The fact that male and female SCD patients display different symptoms is in agreement with currently available literature (Ceglie et al, 2019). Investigating the effects of sex and age on the expression of the disease is important because the manifestations may change with the passing of the years, and because the sexes may experience different numbers or severity of symptoms.…”

Developmental Profile of Sleep and Its Potential Impact on Daytime Functioning from Childhood to Adulthood in Sickle Cell Anaemia

“…Gender differences observed might be attributed to parental and cultural practice, as well as implication of disease severity on health. For example, males with SCA aged 3 months–11 years experienced more pain crises than females per year [ 57 ], which could contribute to the shorter sleep duration observed in our study. Research in a cohort of Chinese children (6–12 years) identified that the strongest predictor for bedtime and waketime in children were school start time, media use, maternal bedtime and waketime, extracurricular activities (e.g., delaying bedtime) and socioeconomic status (e.g., more homework delaying bedtime) [ 58 ].…”

Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways

“…It is likely that this reflects the sickling of red blood cells occurring during the crisis." It would be also interesting to explore the sexual dimorphism of these sickle mice metabolomic signatures, which may explain the sex-related specificity of the clinical expression that has been reported [41].…”

“…However, during the vaso-occlusive crisis in humans, the phosphatidylcholines and lysophosphatidylcholines are mostly increased, while they are drastically reduced in the mouse model in steady state. It is likely that this reflects the sickling of red blood cells occurring during the crisis.” It would be also interesting to explore the sexual dimorphism of these sickle mice metabolomic signatures, which may explain the sex-related specificity of the clinical expression that has been reported [ 41 ].…”