Sickle Cell Disease Children Research Articles

Promising role of Voxelotor in managing sickle cell disease in children: a narrative review

Promising role of Voxelotor in managing sickle cell disease in children: a narrative review

Epidemiological profile of severe malaria and sickle cell disease in children at the mother and child university hospital center Jeanne Ebori foundation of libreville from 2020 to 2021

Background: Hemoglobinopathies represent the most common genetic diseases worldwide. In Gabon, the clinico-biological profile of patients with homozygous hemoglobin S or those with AS sickle cell traits, faced with this prevalence of serious malaria, remains unknown today. The objective was to evaluate the complications of severe malaria in SS homozygous sickle cell patients and those carrying AS sickle cell traits. Methods: This is an observational, retrospective study, with descriptive and analytical aims which took place from January 2020 to October 2021. The parameters studied were socio-demographic, clinical and paraclinical data, the diagnosis chosen, therapeutic data and evolution. Results: severe neurological form of malaria was the most common criterion with a frequency of 41.7%, followed by parasitic forms 35.8% and anemic forms 21.8%. Among AS heterozygotes, the most widespread severe form was the neurological form with a frequency of 63.2%, the anemic form 26.3% and parasitic at 10.5%. In homozygous SS subjects, the most widespread severe form was the anemic form with a frequency of 68.1% followed by neurological forms 27.7% and parasitic forms 4.2%. Abdominal pain, prostration, respiratory distress were the main signs in SS homozygotes. In heterozygotes, prostration, convulsion and clinical jaundice were the main signs. A total of 99.8% of our patients were cured. Conclusions: All the electrophoretic profiles identified were subject to this infection which mainly affects heterozygous AS subjects and subjects with the AA electrophoretic profile in its severe neurological form and homozygous SS subjects in its anemic form.

Vestibular Dysfunction in Patients With Sickle Cell Disease: A Systematic Review.

Sickle cell disease (SCD) often leads to sensorineural hearing loss due to vaso-occlusive events in the cochlear vasculature. Although the vestibule and cochlea share a blood supply, information on vestibulopathy in SCD is limited. This systematic review aims to consolidate current knowledge on vestibular dysfunction in SCD patients. This study, registered on PROSPERO, involved a thorough electronic search using MEDLINE-Ovid, Embase, Google Scholar, The Cochrane Library, and Scopus databases from inception to December 2023. Data extraction adhered to PRISMA guidelines. Authors independently assessed bias and evidence quality using NIH Study Quality Assessment tools. Inclusion criteria covered articles mentioning vestibular symptoms in SCD patients, whereas exclusion criteria comprised non-English articles and vestibular symptoms limited to treatment side effects. Out of 2,495 studies, only 12 met the criteria. Among SCD patients undergoing head imaging, 19% reported inner ear complaints, and 70% experienced dizziness/imbalance. In a group of SCD children, there was a significant relationship between endothelial dysfunction and vertigo duration. The recommended imaging sequence was T1-weighted thin-section temporal bone MRIs, which revealed abnormal findings even without clinical symptoms. Imaging showed labyrinthine hemorrhage and labyrinthitis ossificans, mostly unilateral. Vestibular symptoms emerged with older age, suggesting cortical compensation kept most subjects asymptomatic. In asymptomatic adult SCD patients, there was no significant difference compared with controls in tracking test batteries and positional tests; however, saccadic latency was longer in SCD patients. The existing data on vestibulopathy in SCD were limited and often of poor quality. Although a connection between SCD and vestibular symptoms was noted, information on treatment approaches was scant. Further research in this area could contribute to the early diagnosis of vestibular dysfunction, potentially enhancing outcomes for SCD patients.

Characterizing medical decision-making in sickle cell disease during childhood: Qualitative perspectives of caregivers.

Sickle cell disease (SCD) is the most common genetic disorder among children. As the most common type of SCD, sickle cell anemia (SCA) is associated with severe complications across the lifespan. As parents/caregivers hold primary disease management responsibility during childhood, their involvement in disease management activities, including medical decision-making, is critical to successful and timely management of pediatric SCD. However, the processes through which caregivers make SCD-related decisions remain unknown. The current paper examined caregivers' decision-making processes and priorities when managing their child's SCD. Parents and primary caregivers (N=27) of children with SCA (ages 0-12) completed individual semi-structured qualitative interviews exploring links between caregivers' decision-making and both daily and ongoing SCA management practices. Data were transcribed verbatim, cleaned, systematically coded, and analyzed using applied thematic analysis. Participating caregivers were primarily Black or African American (88.9%), mothers (81.5%), publicly insured (55.6%), and single (51.9%). Caregivers described medical decision-making across acute symptom response, preventive disease management, and treatment initiation and/or discontinuation. Across these contexts of disease management, caregivers overarchingly prioritized protecting and improving their child's quality of life. Caregivers' medical decision-making processes were influenced by their SCA management experience, acquisition of SCA knowledge, and trust in medical providers. The extent to which these influences impacted caregivers' decision-making varied based on disease severity, disease management experience, and time since diagnosis. Findings highlight how processes underlying caregivers' decision-making are directly influenced and informed by caregivers' lived experiences. Future work should develop provider-initiated collaborative interventions to support medical decision-making.

Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.

In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long-term risk of asplenia-related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC-related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with HbSS- and HbAA-RBC, and quantified abnormal RBC by microscopy, spleen-mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were <2%, while proportions of pocked-RBC were 4.3-fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer-containing and homogenous RBC contributed to spleen congestion, resulting in 3.8-fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer-containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine-tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future.

B - 102 Neurocognitive Functioning of Patients Diagnosed with Sickle Cell Disease in Low-to-Middle Income Countries

Abstract Objective Sickle Cell Disease (SCD) is a monogenic blood disorder affecting the production of hemoglobin, a protein that carries oxygen to all vital organs in the body. As a result, insufficient oxygen delivery and cerebrovascular complications often occur which can affect neurocognitive performance. In low-to-middle-income countries (LMIC) where health care and treatment of the disease are harder to access, there is minimal neurocognitive surveillance. Our research aim was to evaluate the neurocognitive impact of SCD in children living in LMIC and establish which neurocognitive assessment measures are commonly used in SCD samples worldwide. Data Selection To analyze this, a librarian created search terms in studies from Embase, PubMed, Web of Science, Global Health CABI, ERIC, CINAHL, and PsycINFO. Studies that focused on participants with SCD of any genotype with a measure for cognitive/academic outcomes were included while commentaries and editorials were excluded. Two research assistants screened 1831 abstracts in Covidence, 52 abstracts were chosen for full-text review, and 18 articles were ultimately included for data extraction. Data Synthesis A systematic review was used to analyze these studies. Most of the studies were conducted in African and Middle Eastern countries and Brazil. Common measures included the Wechsler Intelligence Scale for Children or Adults. Information regarding cultural or language adaptations of neurocognitive measures was rarely reported. Several of the studies demonstrated that individuals with SCD have lower neurocognitive functioning compared to a non-SCD control group. Conclusion Further research is needed regarding the validity of neurocognitive measures used in LMIC among patients diagnosed with SCD.

Lung ultrasound score to predict development of acute chest syndrome in children with sickle cell disease

This study aims to identify lung ultrasound (LUS) findings associated with acute chest syndrome (ACS) at the time of admission and 24-48 h later, to compare these to chest radiography (CXR) findings and to establish a score to predict the development of this pulmonary complication in sickle cell disease (SCD) children METHODS: A prospective observational study of SCD children presenting signs or symptoms of ACS evaluated by LUS and CXR at admission and 24-48 h later. A score was conceived to predict the evolution of ACS during hospitalization based on ultrasonographic findings. Seventy-eight children were evaluated; 61 (78.2 %) developed ACS. A score greater than one at admission showed sensitivity, specificity, accuracy, and positive predictive value (PPV) of 75.4 %, 88.2 %, 78.2 %, and 95.8 %, respectively to predict ACS, while only 32 (52.5 %) CXR showed alterations. The development of ACS during hospitalization was unlikely for a score of zero and very likely for a score greater than one at admission. Regarding follow-up exams, a score greater than one showed sensitivity, specificity, accuracy, and PPV of 98.4 %, 76.5 %, 93.6 %, and 92.8 %, respectively to predict the development of ACS. ACS development was very unlikely for a score of zero and very likely for a score greater than zero in the follow-up. LUS is an effective tool to assess risk for the development of ACS in SCD children with clinical suspicion.

The many faces of sickle cell disease in children: complications in the appendicular skeleton.

Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Musculoskeletal complications of SCD are often the main causes for acute and chronic morbidities in children with manifestations including osteomyelitis, osteoporosis and osteonecrosis. This article aims to familiarise the paediatric radiologist with appendicular skeletal complications of SCD in the paediatric population and their imaging appearance.

Investigation of parental socioeconomic status as a determinant of dietary habits and disease severity of sickle cell disease children

Background: Socioeconomic status (SES) impacts dietary choices and poor dietary pattern has been reported to play a role in the etio-pathogenic mechanisms that give rise to various diseases. Objective: The study is designed to explore the relationship between parental SES and both the dietary habits and disease severity markers among sickle cell disease (SCD) pediatric patients. Methods: Participants’ hemoglobin genotypes and hematocrit levels were determined using standard methods. Questionnaire was administered to the participants to obtain information on qualitative parameters. Descriptive and inferential statistics were used for data analysis. Significant level was set with P &lt; .05. Results: A high percentage of parents of SCD participants were of medium to high SES [73.33%- HbSC; 64.29%- HbSS]. While the rates of hospitalization of HbSS (92.85%) and HbSC (66.67%) were dissimilar, the rates of patients that had suffered vaso-occlusive crisis (VOC) in the last three months prior to the study were comparable [46.67%-HbSC; 53.57%-HbSS]. The daily fruit/vegetable consumption habits of 3 genotypes were poor ranging from 15-25%. The hematocrit levels of the 3 groups were significantly different. Conclusion: The study suggests that high percentage of patients belong to medium-high SES, signifying that educational background of parents did not impact prevalence of the disease.

Sickle Cell Disease and Gut Health: The Influence of Intestinal Parasites and the Microbiome on Angolan Children.

Parasitic infections are a common problem in developing countries and can intensify morbidity in patients with sickle cell disease (SCD), increasing the severity of anemia and the need for transfusions. It has been demonstrated that both helminths and protozoa can affect gut microbiome composition. On the other hand, the presence of specific bacterial communities can also influence parasite establishment. Considering this, our aim was to associate the presence of intestinal parasites with the results of hematological analyses and microbiome composition evaluations in a population of Angolan children with and without SCD. A total of 113 stool samples were collected, and gut microbiome analysis was performed using 16S sequencing and real-time PCR to detect eight different intestinal parasites. In our population, more than half of children (55%) had at least one parasitic infection, and of these, 43% were co-infected. Giardia intestinalis and Ascaris lumbricoides were more frequently found in children from the rural area of Bengo. Moreover, SCD children with ascariasis exhibited higher values of leukocytes and neutrophils, whereas the total hemoglobin levels were lower. In regards to the gut microbiome, the presence of intestinal parasites lowered the prevalence of some beneficial bacteria, namely: Lactobacillus, Bifidobacterium, Cuneatibacter, Bacteroides uniformis, Roseburia, and Shuttleworthia. This study presents the prevalence of several intestinal parasites in a high-risk transmission area with scarce information and opens new perspectives for understanding the interaction between parasites, the microbiome, and SCD.

Relevance of repeated analyses of albuminuria and glomerular filtration rate in African children with sickle cell anaemia.

Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo. Participants were genotyped for apolipoprotein L1 (APOL1) risk variants (RVs) and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. Kidney abnormalities were defined as albuminuria, hyperfiltration or decreased estimated creatinine-based glomerular filtration rate (eGFRcr). At baseline, 247/600 (41.2%) participants presented with kidney abnormalities: 82/592 (13.8%) with albuminuria, 184/587 (31.3%) with hyperfiltration and 15/587 (2.6%) with decreased eGFRcr. After a median follow-up of 5 months, repeated testing was performed in 180/247 (72.9%) available participants. Persistent hyperfiltration and persistent albuminuria (PA) were present in 29.2% (38/130) and 39.7% (23/58) respectively. eGFR normalized in all participants with a baseline decreased eGFRcr. Haemoglobinuria (p = 0.017) and male gender (p = 0.047) were significantly associated with PA and persistent hyperfiltration respectively. APOL1 RVs (G1G1/G2G2/G1G2) were borderline associated with PA (p = 0.075), while HMOX1 long repeat was not associated with any persistent kidney abnormality. This study reveals that a single screening can overestimate the rate of kidney abnormalities in children with SCA and could lead to overtreatment.

Iron incorporation in red blood cells of pediatric sickle cell anemia: a stable isotope pilot investigation.

Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO. SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio-; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method. The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio- patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = -0.775, p = 0.041; SCAio- group: r = -0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio- group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020). SCAio+ group had lower iron incorporation in RBC than SCAio- group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC. This trial was registered at www.ensaiosclinicos.gov.br . Identifier RBR-4b7v8pt.

Serum zinc and magnesium levels in steady state sickle cell children with or without anaemia attending Jos University Teaching Hospital, North-Central Nigeria

Sickle cell anaemia (SCA) is a public health problem. Zinc and Magnesium are essential metal antioxidants important in protection of erythrocytes membrane from oxidative stress; a trigger of vaso- occlusive crisis. This study aims to evaluate the serum levels of zinc and magnesium in steady state sickle cell children with or without anaemia. Comparative cross-sectional study. Forty children aged 1-15 years with sickle cell disease (SCD) in steady state with or without aneamia and 40 age- and- sex matched HbAA counterparts (non-SCD) were consecutively recruited for the study. Each forty SCD and non-SCD children were included in the study. Haemoglobin variants were analysed using haemoglobin electrophoresis. Packed cell volume was determined using haematocrit centrifuge and reader. Serum zinc and magnesium were assayed colorimetrically. Data were analysed using SPSS version 26. Student unpaired t- test was employed to assess the significance of the differences. p-value &amp;#60;0.05 was considered significant. Serum magnesium unlike zinc was significantly (p&amp;#60;0.05) higher in non-SCD group (2.18mg/dl) compared to the SCD group (2.09mg/dl). There was no significant (p&amp;#62;0.05) effect of SCD and anaemia on serum zinc. This study has shown that serum Mg was significantly lower in children with SCD compared to non-SCD counterpart.

Sputum interleukin-6 level as a marker of severity during acute chest syndrome in children with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of morbimortality in sickle cell disease (SCD). In this prospective observational study, we investigated sputum interleukin-6 (IL-6) level as an ACS severity marker during 30 ACS episodes in 26 SCD children. Sputum IL-6 levels measured within the first 72 h of hospitalisation for ACS were significantly higher in patients with oxygen requirement ≥2 L/min, ventilation (invasive and/or non-invasive) length ≥5 days, bilateral and/or extensive opacities on chest X-ray or erythrocytapheresis requirement. Sputum IL-6 could serve as an ACS severity marker to help identify patients requiring targeted anti-inflammatory treatments such as tocilizumab.

Barriers and facilitators to community acceptability of integrating point-of-care testing to screen for sickle cell disease in children in primary healthcare settings in rural Upper East Region of Northern Ghana.

Sickle cell disease (SCD) remains a public health problem especially in sub-Saharan Africa including Ghana. While pilot initiatives in Africa have demonstrated that neonatal screening coupled with early intervention reduces SCD-related morbidity and mortality, only 50-70% of screen-positive babies have been successfully retrieved to benefit from these interventions. Point-of-care testing (POCT) with high specificity and sensitivity for SCD screening can be integrated into existing immunization programs in Africa to improve retrieval rates. This study explored community acceptability of integrating POCT to screen for SCD in children under 5 years of age in primary healthcare facilities in Northern Ghana. This was an exploratory study using qualitative research approach where 10 focus group discussions and 20 in-depth interviews were conducted with community members and health workers between April and June 2022. The recorded interviews were transcribed verbatim after repeatedly listening to the recordings. Data was coded into themes using QSR Nvivo 12 software before thematic analysis. Most participants (70.9%) described SCD as serious and potentially life-threatening condition affecting children in the area. Of 148 community members and health workers, 141 (95.2%) said the screening exercise could facilitate diagnosis of SCD in children for early management. However, discrimination, fear of being tested positive, stigmatization, negative health worker attitude linked with issues of maintaining confidentiality were reported by participants as key factors that could affect uptake of the SCD screening exercise. Most participants suggested that intensive health education (78.3%), positive attitude of health workers (69.5%), and screening health workers not being biased (58.8%) could promote community acceptability. A large majority of participants viewed screening of SCD in children as very important. However, opinions expressed by most participants suggest that health education and professionalism of health workers in keeping patients' information confidential could improve the uptake of the exercise.

Safety and efficacy of monthly high-dose vitamin D3 supplementation in children and adolescents with sickle cell disease

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6 months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28 ng/mL, respectively (P < 0.001)). After 6 months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6 months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = − 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6 months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = − 0.399, P < 0.001). Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts. Trial registration: ClinicalTrials.gov, identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered.What is known:• Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients.• Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL).• Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD.What is new:• We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients.

Evaluation of renal function of sickle cell children in Libreville by estimation of glomerular creatinine-cystatin C filtration rate: prevalence of acute kidney injury and associated factors

Background: Sickle cell disease (SCD) is an important and growing global health problem. Kidney damage is one of the most common complications of SCD. We aimed to determine the prevalence of acute kidney injury (AKI) in children with SCD in our context. Methods: Cross-sectional and analytical study from January 2022 to September 2022, including SCD children aged from 6 months to 17 years during their hospitalisation. We measured the estimated glomerular filtration (eGFR) rate using the combined creatinine and cystatin C formula for kids (CKiDScr-Cys C). Univariate analyses were performed to measure the relationship between variables and AKI and eGFR, followed by a multivariate analysis using logistic regression. Results: Of the 137 children, we included 82 boys (60%) and 55 girls (40%). The mean eGFR was 112±45.3 ml/min/1.73 m2. A total of 36 subjects, or 26.3% (95% CI [18.9-33.6%)), had acute AKI. Comparison of characteristics by AKI status showed significant differences according the number of transfusions (p&lt;0.01), and hemoglobin level (p&lt;0.027), eGFR had a negative correlation with the number of transfusions r=-0.308 (-0.477; -0.117); p&lt;0.01. Multivariate analysis showed that nutritional status was a protective factor of AKI (p&lt;0.01), and the number of transfusions was a predictive factor of AKI in SCD in our context (p&lt;0.001). Conclusions: The results from our study are an urgent alarm to implement the existing management programs on SCD from screening to universal access of hydroxyurea in order to reduce complications and mortality related to this pathology.

New Insights in the Treatment of Sickle Cell Disease in Childhood

Sickle cell disease encompasses diseases that are pathophysiologically caused by hemoglobin S. The HbS component of total hemoglobin in SCD is normally over 50%. HbS is based on an amino acid substitution at position 6 of the β-globin chain, where glutamic acid is replaced by valine. This substitution replaces a hydrophilic amino acid with a hydrophobic amino acid at an outward-facing position in the h molecule, explaining the reduced water solubility and altered molecular organization of HbS compared to normal hemoglobin. Diseases caused by HbS include homozygous SCD, where both alleles are affected by the sickle cell mutation (SCD-S/S), HbSC disease, where one allele is affected by the sickle cell mutation and the other by the HbC mutation (SCD-S/C), and sickle cell β-thalassemia with mixed heterozygosity for the sickle cell mutation and a β-thalassemia mutation (SCD-S/β-thalassemia). In SCD-S/β-thalassemia, forms are distinguished where the β-thalassemia mutation completely inactivates the affected gene (SCD-S/β0-thalassemia) and forms where the allele with the thalassemia mutation still has residual activity (SCD-S/β+-thalassemia). Rarely, the sickle cell mutation can also be combined with other hemoglobin variants (SCD-S/D, SCD-S/OArab, SCD-S/Lepore). The carrier status for the sickle cell mutation generally has no clinical significance except in extreme situations (e.g., eye trauma or surgeries involving cardiopulmonary bypass). Carriers have a normal life expectancy. However, there are individual reports of complications in heterozygous carriers of the sickle cell mutation under common circumstances such as pregnancy, mountain sports, intense physical activity, or air travel. It is also unclear whether the carrier status is associated with an increased rate of kidney complications. Nevertheless, it is not appropriate to indicate specific medical care needs based on these individual case reports given the frequency of carrier status. However, the familial risk of developing SCD should be considered in adult carriers. This manuscript focus on new targets to treat sickle cell anemia in children.

Long-term data from the REACH study testing hydroxyurea to treat sickle cell anaemia in children in sub-Saharan Africa

Long-term data from the REACH study testing hydroxyurea to treat sickle cell anaemia in children in sub-Saharan Africa

Case-control study of heart rate variability and sleep apnea in childhood sickle cell disease.

Obstructive sleep apnea (OSA) is common in sickle cell disease (SCD) despite the absence of overweight, suggesting a specific pathophysiology. We previously showed that otherwise healthy children with increased pharyngeal compliance, a main endotype of OSA, exhibited decreased sympathetic modulation. Our objective was to assess whether modifications of heart rate variability (HRV) and compliance are associated in SCD. Cases (children with SCD, African or Caribbean ethnicity) and controls (otherwise healthy children, same ethnicity), aged 4-18 years, were selected from our database of children referred for OSA and matched for sex, age, and obstructive apnea-hypopnoea index (OAHI) score. The children underwent polysomnography and acoustic pharyngometry (to compute compliance). HRV analyses were performed from 5 min ECG recordings in wakeful, NREM, and REM sleep states and from the whole night. Twenty-one pairs were analysed (median age 10.5 years, 24 girls). Children with SCD had lower BMI z-scores and more tonsil hypertrophy than control children. Children with SCD and OSA (OAHI ≥2/hour) were characterised by lower compliance than children with SCD without OSA. An inverse relationship between compliance and SD2 (HRV from whole night, inversely related to sympathetic modulation) was evidenced (negative relationship in SCD: R = -0.63, p = 0.002 vs. positive relationship in controls R = 0.59, p = 0.006). In conclusion, while the decrease in sympathetic modulation in control children may contribute to increasing pharyngeal compliance, its decrease seems protective in children with sickle cell disease, which underlines the specificity of OSAS pathophysiology in SCD that could be due to sickle cell disease related smooth muscle dystonia.