The role of hydroxyurea in decreasing the occurrence of vasso-occulusive crisis in pediatric patients with sickle cell disease at King Saud Medical City in Riyadh, Saudi Arabia.

OBJECTIVES: To measure the incidence of vaso-occlusive crises (VOC) and the role of hydroxyurea (HU) in reducing VOC in sickle cell anemia  patients being treated at a large tertiary care setting in Kingdom of Saudi Arabia (KSA). The secondary objective of this study is to observe the gradual improvement in laboratory data (white blood cell [WBC], platelets, mean corpuscular volume [MCV], hemoglobin [Hgb], HgbF) following regular use of HU. Methods: Clinical effectiveness of HU was evaluated in a large pediatric population using a retrospective cohort, non-interventional, pre-post treatment study designed to control disease severity selection bias. The cohort included children with SCA (sickle cell (SS), sickle-beta thalassemia) at King Saud Medical City, Riyadh, KSA, who initiated HU between January 2012 and June 2017. For each patient healthcare utilization, laboratory values, and clinical outcomes were observed for an equal duration of time pre and post hydroxyurea. Results: Out of 416 SCD patients, 128 children with SCD who initiated HU, of them 82 met the eligibility criteria. After initiation of HU, there was significant reduction in both VOC (80%) and length of stay (LOS) (73%). Significant increase in Hgb (13%), MCV (10%), and HgbF (28%) and significant decrease in WBC (28%) was observed. Only the mean platelet count decreased by 3% with a p greater than 0.05. Conclusion: Hydroxyurea treatment significantly decreased episodes of VOC and LOS, it also led to reductions in hospitalizations and significant improvement in complete blood count indices.

Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation.

BACKGROUND: Split hand and foot malformation (SHFM) refers to a genetically heterogeneous developmental disorder of the hands and feet that presents as median ray deficiency of varying severity. 7q21.3 (SHFM1) is one of six loci described to date, and although DLX5 and DLX6 are compelling candidates in that locus, no intragenic mutations have been described in either of these genes. METHODS: The authors combined autozygome analysis and exome sequencing to study a consanguineous family with a highly unusual SHFM phenotype, where there is associated dorsalisation of the hands. RESULTS: A novel missense mutation in a highly conserved residue of the homeobox domain of DLX5 was identified. Unlike previously reported position effect mutations in SHFM1, this first documented intragenic DLX5 mutation is also accompanied by abnormal dorsal-ventral patterning. CONCLUSION: This study identified the first intragenic DLX5 mutation in SHFM and raises interesting possibilities about a dual role for DLX5 in limb development.