ANTXR1 Intronic Variants Are Associated with Fetal Hemoglobin in the Arab-Indian Haplotype of Sickle Cell Disease.

Disease severity of sickle cell anemia is highly variable, and it is commonly accepted that fetal hemoglobin (HbF) levels play a major role as an ameliorating factor. Investigation of genetic variants have identified several genes to be the principal influencers of HbF regulation. Here, we further elucidated the association of rs4527238 and rs35685045 of ANTXR1 genes in the context of HbF level variance in sickle cell anemia patients of the Arab-Indian haplotype. Samples from 630 sickle cell anemia patients were analyzed for the mutations at 2 specific locations of the ANTXR1 gene by TaqMan®-based real-time PCR. The CC genotype (p = 0.018) of rs4527238 and the TT genotype (p = 0.048) of rs35685045 of ANTXR1 were found to be significantly associated with low HbF expression. The frequency of the CC genotype of rs4527238 was observed to be high in the low HbF patient group compared to the high HbF group (p = 0.009). Likewise, the frequency of the TT genotype of rs35685045 was also high among the low HbF group (p = 0.017). The ANTXR1 genetic mutations and the association with HbF expression in the Arab-Indian haplotype sickle cell patients revealed that the ANTXR1 gene may be a major HbF modulator leading to potential therapeutic options that should be further explored.

Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab-Indian haplotype is not benign.

Sickle cell disease (SCD) in Saudi patients from the Eastern Province is associated with the Arab-Indian (AI) HBB (ß-globin gene) haplotype. The phenotype of AI SCD in children was described as benign and was attributed to their high fetal haemoglobin (HbF). We conducted a hospital-based study to assess the pattern of SCD complications in adults. A total of 104 patients with average age of 27 years were enrolled. Ninety-six per cent of these patients reported history of painful crisis; 47% had at least one episode of acute chest syndrome, however, only 15% had two or more episodes; symptomatic osteonecrosis was reported in 18%; priapism in 17%; overt stroke in 6%; none had leg ulcers. The majority of patients had persistent splenomegaly and 66% had gallstones. Half of the patients co-inherited α-thalassaemia and about one-third had glucose-6-phosphate dehydrogenase deficiency. Higher HbF correlated with higher rate of splenic sequestration but not with other phenotypes. The phenotype of adult patients with AI SCD is not benign despite their relatively high HbF level. This is probably due to the continued decline in HbF level in adults and the heterocellular and variable distribution of HbF amongst F-cells.

Primary myelofibrosis with concurrent paroxysmal nocturnal haemoglobinuria presenting with erectile dysfunction.

Primary myelofibrosis and paroxysmal nocturnal haemoglobinuria (PNH) are uncommon clonal blood disorders that are rarely found together. We report a case of primary myelofibrosis (PMF) with concomitant subtle PNH in a 42-year-old man who presented with a 4-week history of fatigue, unexplained chest pain, and new-onset erectile dysfunction. Bone marrow biopsy showed severe fibrosis consistent with PMF. However, smooth muscle dystonia symptoms in the form of new-onset erectile dysfunction and oesophageal spasm were not fully explained by PMF but were clues for PNH, confirmed by flow cytometric assays. Routine PNH testing for patients with new-onset PMF and clinical symptoms suggestive of PNH, as well as those with refractory anaemia despite effective therapy, is crucial since these two conditions can coexist. As a result, a lack of early testing may cause a delay in diagnosis, increasing the patient's transfusion load and the facility's costs.

Chronic myelogenous leukemia in sickle cell/beta 0-thalassemia.

Sickle cell/beta (0)-thalassemia (S/ß(0)-thal) is a compound heterozygous state for ßS and ß(0) thalassemia. There are rare reported cases of patients with sickle cell disease who developed hematological neoplasms including myeloid and lymphoid conditions; however, to the best of our knowledge, chronic myelogenous leukemia (CML) occurring in S/ß(0) -thal has been reported in one case and this is the second such report.