Does Sickle Cell Disease Protect Against Diabetes Mellitus?: Cross-sectional study.

Objectives: The co-existence of diabetes mellitus (DM) and sickle cell disease (SCD) is rare. This study aimed to explore whether SCD patients have the same DM prevalence as the general population in a country with a high prevalence of DM. Methods: This cross-sectional study included all SCD adult patients admitted to Salmaniya Medical Complex, Bahrain, between 2003 and 2010 (n = 2,204). A random sample (n = 520) was taken to establish the prevalence of DM. Laboratory records were examined to determine the presence of DM. Results: There were 376 SCD patients with complete records; of these, 24 (6.4%) had DM. The age- and sex-standardised prevalence of DM was 8.3%. Conclusion: While the prevalence of DM in SCD patients in Bahrain was high, it was lower than expected in this population. SCD may have a protective effect towards DM development. However, the impact of these two conditions on vascular diseases suggest a need for screening and aggressive treatment in this population.

Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10.

Dyskeratosis congenita (DC) is characterized by multiple features including mucocutaneous abnormalities, bone marrow failure and an increased predisposition to cancer. It exhibits marked clinical and genetic heterogeneity. DKC1 encoding dyskerin, a component of H/ACA small nucleolar ribonucleoprotein (snoRNP) particles is mutated in X-linked recessive DC. Telomerase RNA component (TERC), the RNA component and TERT the enzymatic component of telomerase, are mutated in autosomal dominant DC, suggesting that DC is primarily a disease of defective telomere maintenance. The gene(s) involved in autosomal recessive DC remains elusive. This paper describes studies aimed at defining the genetic basis of AR-DC. Homozygosity mapping in 16 consanguineous families with 25 affected individuals demonstrates that there is no single genetic locus for AR-DC. However, we show that NOP10, a component of H/ACA snoRNP complexes including telomerase is mutated in a large consanguineous family with classical DC. Affected homozygous individuals have significant telomere shortening and reduced TERC levels. While a reduction of TERC levels is not a universal feature of DC, it can be brought about through a reduction of NOP10 transcripts, as demonstrated by siRNA interference studies. A similar reduction in TERC levels is also seen when the mutant NOP10 is expressed in HeLa cells. These findings identify the genetic basis of one subtype of AR-DC being due to the first documented mutations in NOP10. This further strengthens the model that defective telomere maintenance is the primary pathology in DC and substantiates the evidence in humans for the involvement of NOP10 in the telomerase complex and telomere maintenance.

Trisomy 4 as the sole karyotypic abnormality in a case of acute biphenotypic leukemia with T-lineage markers in minimally differentiated acute myelocytic leukemia.

We report an unusual case of acute biphenotypic leukemia with trisomy 4. A 22-year-old woman presented with acute leukemia characterized by the presence of two cell populations (prothymocytic and myeloblastic). The leukemic cells were resistant to standard induction chemotherapy and were cleared from the bone marrow only after a salvage chemotherapy regimen. To our knowledge, this is the fourth reported case of acute biphenotypic leukemia with trisomy 4 and perhaps the first case with T-lineage markers and acute myelocytic leukemia.