Three siblings with variable degrees of neuromuscular involvement and congenital sideroblastic anemia: A peculiar phenotype and a surprise genotypic explanation.

INTRODUCTION: Congenital sideroblastic anemias (CSAs) are a group of inherited bone-marrow disorders manifesting with erythroid hyperplasia and ineffective erythropoiesis. METHODS: We describe a detailed clinical and genetic characterization of three siblings with CSA. RESULTS: Two of them had limb-girdle myopathy and global developmental delay. The two elder siblings performed allogenic hematopoietic stem-cell transplantation 5 and 3 years prior with stabilization of the hematological features. Exome sequencing in the non-transplanted sibling revealed a novel homozygous nonsense variant in SLC25A38 gene NM_017875.2:c.559C > T; p.(Arg187*) causing autosomal-recessive sideroblastic anemia type-2, and a second homozygous pathogenic previously reported variant in GMPPB gene NM_013334.3:c.458C > T; p.(Thr153Ile) causing autosomal-recessive muscular dystrophy-dystroglycanopathy type B14. With the established diagnosis, hematopoietic stem cell transplantation is now being scheduled for the youngest sibling, and a trial therapy with acetylcholine esterase inhibitors was started for the two neurologically affected patients with partial clinical improvement. CONCLUSION: This family emphasizes the importance of whole-exome sequencing for familial cases with complex phenotypes and vague neurological manifestations.

Transcranial Doppler Velocities among Sickle Cell Disease Patients in Steady State.

Transcranial Doppler (TCD) screening is an established tool to identify children with sickle cell disease at high risk of stroke. Our objective was to study TCD velocities among sickle cell disease patients while in a steady state. This cross-sectional study included 78 steady state sickle cell disease patients [31 Hb SS (ßS/ßS) (sickle cell anemia), 47 Hb S/ß-thalassemia (HBB: c.20A>T/ß-thal)], attending the Pediatric Hematology Clinic at Cairo University Children's Hospital, Cairo, Egypt. All patients underwent TCD velocity assessment as per the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. In our cohort, TCD velocities were comparable among Hb S/ß-thal vs. SS patients. Hemolysis indicators correlated significantly to TCD velocities in Hb S/ß-thal patients; positive correlation was found between total bilirubin level and right middle cerebral artery (MCA) and right distal internal carotid artery (dICA) TCD velocities (r = 0.428, p = 0.00, r = 0.360, p = 0.01), respectively as well as between reticulocyte count and right MCA, right dICA and right anterior cerebral artery (ACA) TCD velocities (r = 0.424, p = 0.01), (r = 0.40, p = 0.00), (r = 0.303, p = 0.04), respectively. On the other hand, statistically significant negative correlations were found between hemoglobin (Hb) level and right ACA, right dICA TCD velocities (r = -0.290, p = 0.05), (r = -0.324, p = 0.03). Although Hb F is considered an ameliorating factor for disease severity; hemolysis stands as an indicator of risk for TCD velocity elevation, and in turn, risk for stroke among sickle cell disease patients.