Hematological characteristics and hepatobiliary complications of hereditary spherocytosis in a tertiary care pediatric center: optimizing diagnosis and care through local and international networks.

Background: Hereditary Spherocytosis (HS) is a rare, congenital red blood cell disorder presenting with variable clinical manifestations ranging from mild hemolytic anemia to severe anemia with hypersplenism and hepatobiliary complications. Methods: The objectives of the study were to evaluate the diagnostic pathway of HS, the presence and management of hepatobiliary complications in pediatric patients with HS followed in a tertiary care center. The demographic, clinical, hematological information were retrieved from medical records of patients having at least 1 hematology visit between 2010 and 2020. Results: Forty-two patients were enrolled, 23 M. Mean age at onset of symptoms was 2.8 years, at diagnosis was 3.5 years. Anemia was the first manifestation in 73%; suspect of HS arose for all patients in first or second level outpatient clinics. Only 64% of patients performed two confirmation tests in the reference center. 28/42 had familiarity for HS; of the 13/42 who did not, only 47% performed further analysis. Sixteen patients developed gallbladder stones (40%), visible at the first ultrasound (5.6 years). Hemolytic crises and parvovirus infections were more frequent in patients with stones (53.6% vs. 26.1% and 63.6% vs. 28.6%, respectively). 10/16 (62.5%) underwent elective cholecystectomy: 8 had concomitant splenectomy. Conclusions: our study highlights the need to optimize the diagnostic pathway in networks of care involving general and specialized centers in order to reduce time to diagnosis and ensure that all patients receive confirmatory tests. A high frequency of hepatobiliary complications since young age was observed suggesting that screening with ultrasound should begin earlier.

Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children with sickle cell disease: Results from a long-term natural history study in Italy in the era of multimodal therapy.

BACKGROUND: Stroke and cerebral vasculopathy are leading causes of morbidity and mortality in patients with sickle cell disease (SCD). Transcranial Doppler (TCD) is a reliable and validated predictor of stroke risk. Children with conditional or abnormal TCD are at an increased risk for stroke, which can be mitigated by red blood cell transfusion or hydroxyurea. Elucidating the relationship between cerebral hemodynamics and hemolytic anemia can help identify novel therapeutic approaches to reduce stroke risk and transfusion dependence. METHODS: This long-term, real-world study was designed to evaluate the prevalence of TCD imaging (TCDi)-assessed flow velocities in children and to interrogate their relationship with markers of anemia and hemolysis. RESULTS: In total, 155 children (median follow-up 79.8 months, 1358.44 patient-years) had 583 evaluable TCDi results. Only patients with HbSS or HbSß0 had abnormal (1.6%) or conditional (10.9%) TCDi. Children with abnormal or conditional TCDi had lower hemoglobin (Hb) and higher hemolysis markers. A linear correlation was detected between TCD velocity and Hb: an Hb increase of 1 g/dL corresponded to decreases in velocity in the internal carotid and middle cerebral arteries (6.137 cm/s and 7.243 cm/s). Moreover, patients with Hb >9 g/dL presented a lower risk of TCDi-associated events. CONCLUSION: These results support the need to optimize disease-modifying treatments that increase Hb and reduce hemolysis for stroke prevention in young children with SCD.

Point-of-care testing allows successful simultaneous screening of sickle cell disease, HIV, and tuberculosis for households in rural Guinea-Bissau, West Africa.

Diagnosis of noncommunicable genetic diseases like sickle cell disease (SCD) and communicable diseases such as human immunodeficiency virus (HIV) or tuberculosis (TB) is often difficult in rural areas of Africa due to the lack of infrastructures, trained staff, or capacity to involve families living in remote areas. The availability of point-of-care (POC) tests for the above diseases offers the opportunity to build joint programs to tackle all conditions. We report successful simultaneous screening of SCD, HIV, and TB utilizing POC tests in 898 subjects in Fanhe, in rural Guinea-Bissau. Adherence was 100% and all diagnosed subjects were enrolled in care programs.

Distribution of HbS Allele and Haplotypes in a Multi-Ethnic Population of Guinea Bissau, West Africa: Implications for Public Health Screening.

Background: Sickle Cell Disease (SCD) is an inherited condition that is widespread globally and especially in malaria-endemic West African countries. Limited epidemiological data on SCD are available for Guinea Bissau, where newborn screening is not yet implemented, routine diagnosis is not available, and care is case directed. Methods: Dried blood spots were collected from children accessing two hospitals managed by Italian Non-Governmental Organizations in the capital city of Bissau and sent to Padova for Hemoglobin (Hb) quantification through HPLC and molecular analysis. Beta globin gene analysis was performed in all; and Hb haplotype of the HbSS and HbSA patients was performed in South Africa. One hundred samples belonging to the most frequent ethnic groups were randomly selected for detection of G6PD mutations. Results: Samples from 848 consecutive children (498 males and 350 females, mean age 6.8 years) accessing the two hospitals were analyzed: 6.95% AS (4.42% allelic frequency), 0.94% SS, and 0.23% AC. 376G G6PD allelic frequency was 24%; 14.8% in AS individuals. The Senegal haplotype was the most prevalent (31%), and the proposition of chromosomes with the atypical haplotype was surprisingly high (56%). Conclusion: Our study demonstrates a significant frequency of the HbS allele in the population of Guinea Bissau supporting the implementation of screening strategies. The differences among ethnic groups can help guide targeted interventions for SCD awareness campaigns and determine priority areas for public health interventions. The pilot analysis on haplotypes reveals a large proportion of the atypical haplotype, which may be indicative of a genetically heterogeneous population.

Visual cortex changes in children with sickle cell disease and normal visual acuity: a multimodal magnetic resonance imaging study.

The visual system is primarily affected in sickle cell disease (SCD), and eye examination is recommended starting in late childhood. So far, to our knowledge, all studies have focused on the retina, neglecting the changes that might be present in the cortical portion of the visual system. We performed a multimodal magnetic resonance imaging (MRI) evaluation of the visual cortex in 25 children with SCD (mean age: 12·3 ± 1·9 years) and 31 controls (mean age: 12·7 ± 1·6 years). At ophthalmologic examination, 3/25 SCD children had mild visual acuity deficits and 2/25 had mild tortuosity of the retinal vessels. None showed optic pathway infarcts at MRI or Transcranial Doppler abnormal blood velocities, and 6/25 disclosed posterior cerebral artery stenosis (five mild and one severe) at MR-angiography. Compared to controls, SCD children had increased posterior pericalcarine cortical thickness, with a different trajectory of cortical maturation and decreased connectivity within medial and ventral visual neural networks. Our findings suggest that SCD affects the development and the tuning of the visual cortex, leading to anatomical and functional changes in childhood even in the absence of retinopathy, and set the basis for future studies to determine if these changes can represent useful predictors of visual impairment in adulthood, biomarkers of disease progression or treatment response.