Should we screen for hereditary hemochromatosis in healthy Lebanese: a pilot study.

Hereditary hemochromatosis (HHC) is a genetic disorder of iron metabolism characterized by abnormal accumulation of iron that may lead to organ damage and death. Diagnosis is usually based on various genetic and phenotypic criteria. The study goals were to perform mutation analysis for 18 different mutations associated with HHC in healthy Lebanese, determine their allele frequency, and compare iron-overload status in identified carriers versus those found to be wild-type for mutations analyzed. 116 healthy adults (59 males and 57 females) underwent DNA testing for 18 different HHC mutations, and biochemical testing for percent transferrin saturation (%TS) and ferritin. C282Y mutation was not detected. Only H63D mutation (rs1799945) was found with an overall carrier frequency of 25.8% (24.1% heterozygous and 1.7% homozygous). %TS and ferritin differed significantly between genders. %TS and ferritin were significantly higher in males with H63D mutation when compared to males with wild-type (P=0.001, 0.019; respectively); but not in females. The proportion of subjects with increased %TS and serum ferritin was not statistically different between those with H63D mutation and the wild-type in either gender. In addition, none of the subjects had concurrent increase in %TS and ferritin. In conclusion, the H63D carrier frequency in healthy Lebanese is comparable to other populations in the region, and it does not result in significant biochemical iron overload. Moreover, in the absence of the C282Y mutation, genetic screening for HHC is not recommended according to this preliminary study in healthy Lebanese.

Comparison of neutrophil volume distribution width to C-reactive protein and procalcitonin as a proposed new marker of acute infection.

BACKGROUND: The aim of this study was to assess the use of neutrophil distribution width (NDW) and to compare it to C-reactive protein (CRP) and procalcitonin (PCT), in the detection of early sepsis in the intensive care unit. METHODS: Subjects (N = 166) were divided into 4 groups: healthy, acute inflammatory non-infectious (AINI), localized infection, and systemic infection, according to clinical history and cultures. NDW, CRP, and PCT were compared among the different groups using multivariate analysis of variance (MANOVA). Diagnostic efficacy was assessed using receiver operating characteristic curves and areas under the curves (AUC). RESULTS: The lowest mean(NDW) was found in the healthy group (n = 41), followed by the AINI (n = 20), localized infection (n = 55), and systemic infection (n = 50) groups. AUC(NDW) was 0.877 for infected (localized + systemic) vs non-infected (healthy + AINI) groups, and 0.965 for systemic infection vs non-infected groups. A cut-off of 21.9 resulted in 90% sensitivity, 92% specificity, 90% positive predictive value, and 92% negative predictive value (AUC(NDW) = 0.965, 95% confidence interval 0.935-0.995). According to MANOVA, only NDW was able to differentiate an acute inflammatory process from early infection in postoperative patients, but not healthy from AINI subjects. CONCLUSIONS: NDW had the highest diagnostic accuracy and is available with the complete blood count with differential (CBC). It may be a promising parameter to aid in the diagnosis of acute infection in adults, provided the possibility of haematological disorders is first ruled out.

Chronic lymphocytic leukemia associated with myelodysplastic syndrome with ring sideroblasts.

Diagnosis of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and chronic lymphocytic leukemia (CLL) in the same patient is extremely rare. We describe a 69-year-old CLL patient who developed MDS with ring sideroblasts 1 year after diagnosis of CLL and without any previous treatment. Diagnosis was based on flow cytometry, bone marrow aspirate morphology, and iron stain. Our findings indicate that the 2 disorders belong to 2 different hematopoietic clones in this patient. In cases of worsening anemia in CLL patients, it is recommended that an iron stain be performed on bone marrow aspirates to exclude a coexistent malignancy such as refractory anemia with ring sideroblasts.

Apolipoprotein E gene polymorphisms in Lebanese with hypercholesterolemia.

Apolipoprotein E (ApoE) has an important role in the metabolism of lipids through its major isoforms (ε2, ε3, ε4). In particular, ApoE ε4, has been considered as a major genetic risk factor for cardiovascular diseases (CVD). The aim of our study is to investigate the frequency of ApoE gene polymorphisms (rs 429358C>T, rs 7412C>T) and their relationship to lipid parameters in a group of Lebanese hypercholesterolemic subjects (22 males and 24 females, aged 25-80 years). Lipid profile, apolipoproteins A-I and B were determined using fasting serum samples; and molecular analysis of ApoE polymorphisms using blood in EDTA tubes. The distribution of the four ApoE genotypes detected in this study was: ε3/ε3 (73.9%), ε3/ε4 (17.4%), ε2/ε3 (6.5%), and ε2/ε4 (2.2%) resulting in allelic frequencies for ε2, ε3 and ε4 of 4.3%, 85.9% and 9.8%, respectively. No association was determined among any of the lipid parameters, gender and ApoE genotypes. Lipid parameters were not statistically different among various ApoE genotypes (p>0.05). ApoE ε2 frequency was found to be lower than that previously reported for healthy Lebanese (7.2%). CVD is one of the major leading causes of mortality in Lebanon with a reported prevalence of 12.2% in males and 7.7% in females, which incidentally agrees with our finding regarding ε4 allelic frequency of 13.6% in males and 6.3% in females. Consequently, larger prospective studies are recommended to highlight the correlation of ApoE polymorphisms to other biochemical and environmental factors involved in CVD.

Extended use of serum free light chain as a biomarker in lymphoproliferative disorders: a comprehensive review.

Serum free light chain (sFLC) assays were shown to improve detection, management, and prognostication in plasma cell disorders. Recently, sFLC assays improved detection of M proteins when combined with standard methods of protein electrophoresis/immunofixation in patients with non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL). Incidence of abnormal sFLC ratio (sFLCr) varied from 0% to 36% and 29.7% to 59% in NHL and CLL, respectively. Increased sFLC levels or abnormal sFLCr predict shorter overall survival in early-stage CLL. Furthermore, abnormal sFLCr correlated with advanced disease stage and poorer outcome. In diffuse large B-cell lymphomas, increased sFLC was demonstrated as an independent, adverse prognostic factor for overall/event-free survival. Moreover, abnormal sFLCr can be a diagnostic tool in central nervous system lymphomas. Finally, the quantitative FLC assay has the potential to become a new, easily measured biomarker for predicting prognosis and enhanced detection in NHL/CLL. It may be used serially at follow-up evaluations to provide clues to relapse.

Correlation of methylenetetrahydrofolate reductase polymorphisms with homocysteine metabolism in healthy Lebanese adults.

Hyperhomocysteinemia is associated with several vascular and teratogenic conditions. Determinants of total homocysteine concentrations include genetic and nutritional factors. This study assesses the relation between homocysteine concentrations and MTHFR gene polymorphisms at two common alleles (C677T (rs1801133) and A1298C (rs1801131)) as well as other predictors of homocysteine (folate, vitamin B(12), body mass index (BMI), age, and gender) in a group of healthy Lebanese: 109 males and 124 females aged 17-55years. We used serum for the determination of homocysteine, folate and vitamin B(12) levels and blood drawn in EDTA tubes for molecular analysis of MTHFR polymorphisms. Hyperhomocysteinemia was present in 59/233 (25.3%) of the subjects, with male/female ratio of 1.95. Multivariable regression analysis showed that homocysteine levels were negatively related to folate and vitamin B(12) and positively related to male gender and C677T homozygosity; but not A1298C polymorphism, BMI or age. The prevalence of wild, heterozygous, and homozygous C677T genotypes was 45.0%, 43.3% and 11.6%, respectively; with a carrier frequency of 54.9% and allelic frequency of 33.3%. The A1298C genotypic prevalence was 39.5%, 30.9%, and 29.6% respectively; with a carrier frequency of 60.5% and allelic frequency of 45.1%. C677T/A1289C compound heterozygosity was present in 47/233 (20.2%) of volunteers. In this first pilot study, gender, folate, vitamin B(12) and C677T mutational status could explain around 32% of homocysteine variations. Future larger studies are recommended to investigate other predictors of homocysteine variation and combine them with markers explored in this and other studies, in order to evaluate their impact on vascular and/or congenital diseases.

The use of a reverse hybridization strip assay for the study of hemochromatosis-associated gene mutations in Lebanon.

AIMS: Hereditary hemochromatosis (HHC) is the most commonly identified autosomal recessive genetic disorder in the Caucasian population and HFE gene mutations are highly concentrated among European populations. This is the first study that screens for HHC-related gene mutations in a healthy Lebanese sample population. METHODS: Using the reverse hybridization Hemochromatosis StripAssay A from ViennaLab, the DNA extracted from a total of 116 healthy volunteers (59 males and 57 females) was analyzed, looking for 18 different mutations in the HFE, ferroportin, and transferrin genes. RESULTS: For the HFE gene, the C282Y mutation was not detected, but the H63D mutation was found with an overall carrier frequency of 25.8% (24.1% heterozygous and 1.7% homozygous). None of the mutations in the transferrin and ferroportin genes was identified. CONCLUSIONS: The Hemochromatosis StripAssay A from ViennaLab provides an easy and reliable technique for simultaneous screening of the different HFE gene mutations. This first study in Lebanon represents a baseline report for further future studies in the field using this easy technique with a reasonable turnaround time for diagnosis. We also note that ferroportin and transferrin gene mutations have not been detected in this population sample and larger clinical studies will be needed to better estimate their prevalence.

Massive pulmonary embolism associated with Factor V Leiden, prothrombin, and methylenetetrahydrofolate reductase gene mutations in a young patient on oral contraceptive pills: a case report.

Factor V Leiden (Factor V G1691A), prothrombin gene mutation G20210A, and homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene are known to predispose venous thromboembolism (VTE). We present herein a rare case of a young woman heterozygous for these mutations and taking oral contraceptive pills for less than 2 months, diagnosed to have massive deep venous thrombosis and bilateral pulmonary embolism. The patient was managed for 10 days in the hospital and discharged home on oral anticoagulants. This case suggests that screening for these factors in people with family history of thrombosis and in relatives of patients with these mutations is highly recommended to prevent fatal consequences. In addition, a new guideline for treatment and prophylaxis with anticoagulant for these patients and others who are at risk of developing VTE (American College of Chest Physicians [ACCP] guidelines-Chest 2008) has been published recently. Our recommendation is to promote for the internationally published algorithms through their application, where necessary, to prevent any future thrombotic morbidity or mortality incidents.

Essential thrombocythemia with myelofibrosis transformed into acute myeloid leukemia with der(1;15)(q10;q10): case report and literature review.

Translocations involving chromosomes 1 and 15 are uncommon in hematologic malignancies. So far, only 42 cases have been reported with t(1;15) as a reciprocal or complex chromosomal abnormalities. We herein report the first case in the literature, to our knowledge, of a 44-year-old female with essential thrombocythemia and severe myelofibrosis who developed acute myeloid leukemia (AML-M4) with der(1;15)(q10;q10) after 13 years of treatment. In addition, we reviewed the literature for all up-to-date published cases with t(1;15).

Long-term outcome of adult acute lymphoblastic leukemia in Lebanon: a single institution experience from the American University of Beirut.

BACKGROUND AND OBJECTIVES: The most important studies about outcome of acute leukemia come from developed countries, whereas most of the patients with this disease are in developing countries. We report predictive and prognostic factors in patients with acute lymphoblastic leukemia (ALL) in a tertiary care center in a developing country. PATIENTS AND METHODS: We retrospectively reviewed the records of adult patients with acute leukemia who were referred to the American University of Beirut Medical Center between 1996 and early 2006. RESULTS: Of 105 patients, 36 (34%) patients were diagnosed with ALL, and included 19 (53%) males and 17 (47%) females with a median age of 34 years (range, 14-79 years). Induction chemotherapy with curative intent was administered to 34 (94%) patients. Twenty-seven patients received intrathecal chemotherapy as prophylaxis (n=24) or as treatment for CNS disease (n=3). Twenty-eight patients (82%) achieved complete remission (CR) after induction chemotherapy. The median overall survival (OS) time was 22 months and the five-year OS for ALL patients was 38%. The median disease-free survival (DFS) time was 12 months, while the five-year DFS was 38%. Multivariate analysis showed that age <40 years, WBC <30 X 109/L, achievement of CR after first induction, and CNS prophylaxis were predictive factors for OS and DFS. CONCLUSION: Despite limitations and the relatively low socioeconomic status of the Lebanese population, OS (38%) and DFS (38%) are quite similar to international data. Trends toward a higher CR and DFS in adults are due to intensified consolidation chemotherapy, the use of stem cell transplantation, and improvements in supportive care.