Abdulkareem Al-Momen

LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency

BACKGROUND Clinical immunology has traditionally relied on accurate phenotyping of the patients immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis. OBJECTIVE We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency. METHODS We performed exome sequencing followed by autozygome filtration. RESULTS A truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family. CONCLUSION The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.

Intravenous iron sucrose complex in the treatment of iron deficiency anemia during pregnancy

OBJECTIVE To evaluate the safety and efficacy of intravenous iron sucrose complex (ISC) as compared with oral ferrous sulfate in the treatment of iron deficiency anemia during pregnancy. STUDY DESIGN prospective, open, controlled study in which pregnant women with iron deficiency anemia were sequentially selected from the antenatal clinic and assigned either to ISC (study group) or to ferrous sulfate (control group). METHODS Each study patient was given the total calculated amount of ICS (Hb deficit (g/l) x body weight (kg) x 0.3) in divided doses (200 mg (elemental iron) in 100 ml normal saline intravenously over 1 h daily) followed by 10 mg/kg to replenish iron stores. Each patient of the control group was given ferrous sulfate 300 mg (60 mg elemental iron) orally three times a day. All patients were monitored for adverse effects, clinical and laboratory response. RESULTS There were 52 patients and 59 controls. ISC group achieved a significantly higher Hb level (128.5 +/- 6.6 g/l vs. 111.4 +/- 12.4 g/l in the control group P < or = 0.001) in a shorter period (6.9 +/- 1.8 weeks vs. 14.9 +/- 3.1 weeks in the control group, P < or = 0.001). ISC complex group showed no major side effects while 4 (6%) of the control group could not tolerate ferrous sulfate, 18 (30%) complained of disturbing gastrointestinal symptoms and 18 (30%) had poor compliance. CONCLUSION We conclude that ISC is safe and effective in the treatment of iron deficiency anemia during pregnancy.

Effect of recombinant human erythropoietin on lymphocyte phenotyping and phagocyte activity in hemodialysis patients

The effect of recombinant human erythropoietin (rHmEPO) on lymphocytic phenotyping as well as on the phagocyte activity of polymorphonuclear cells and monocytes was evaluated in 16 patients on maintenance hemodialysis. The mean age of the patients was 38.2 +/- 16.2 years. There were seven men and nine women. All patients were started on 50 U/kg of rHmEPO intravenously three times per week, and the dosage was increased gradually to achieve target haemoglobin of 12 g/dL. Predialysis blood samples were taken monthly for 3 months, and phagocyte respiratory burst as well as lymphocyte subsets were studied. Healthy blood donors were taken as controls. By 3 months of rHmEPO treatment, there was no significant increase in total T and B cells, but there was a significant increase in both CD4 (P < 0.001) and CD8 (P < 0.005): however, there was no significant change in the CD4/CD8 ratio. There was significant reduction in the natural killer cells (P < 0.005). The phagocyte activity studies showed a significant increase in the respiratory burst in whole blood (P < 0.001) and opsonized zymosan (P < 0.001) as well as improvement in the suppressed polymorphonuclear cell and monocyte activity by uremia. Phagocytosis studied by yeast uptake showed significant improvement from the pretreatment suppressed phagocytes to normal activity posttreatment. In conclusion, treatment with rHmEPO increases CD4 and CD8 cell counts without affecting the CD4/CD8 ratio, decreases the natural killer cells, and improves the impaired phagocyte activity in hemodialysis patients.

HYPOCALCEMIA DUE TO HYPOPARATHYROIDISM IN β-THALASSEMIA MAJOR PATIENTS

BACKGROUND This is a retrospective analysis of case records of β-thalassemia major patients who developed hypoparathyroidism (HPT). The objective of this study was to assess the prevalence of hypoc...

The Pharmacological Manipulation of Fetal Haemoglobin: Trials Using Hydroxyurea and Recombinant Human Erythropoietin

Hydroxyurea (HU) and recombinant human erythropoietin (rHuEpo) have been used in several studies to elevate Hb F level in sickle cell disease (SCD) patients and hence to ameliorate the clinical presentations of the disease. The treatment protocol and doses have varied in the different studies. We studied the effects of HU+rHuEpo combination therapy in sickle cell anaemia (SCA patients) to investigate the Hb F manipulation and hence treatment of SCA. Six patients with severe SCA were selected for treatment with HU (20-25 mg/kg body weight) and rHuEpo (400-800 U/kg body weight) combination therapy for 4 weeks followed by HU (20-25 mg/kg body weight) maintenance therapy for 6 months to 1 year. Iron and folic acid were administered during HU+rHuEpo treatment. Signs, symptoms and complications were recorded to obtain the severity index. Only patients with a severity index > or = 6 were included in the study. Haematological and biochemical parameter values, Hb A2, Hb F, Hb F distribution, Hb F cells, bilirubin level and reticulocyte count were assessed at least on 2-3 occasions prior to initiation of the therapy protocol to establish baseline values. During the treatment period, the clinical presentations were monitored and the estimation of the laboratory parameters was carried out every 4-8 weeks. The results of these parameters during HU and rHuEpo combination therapy and HU maintenance therapy were compared with baseline values using paired t test. The elevation in the level of Hb F, Hb F cells, total haemoglobin, red cell count and MCV were significant (p < 0.005), while reticulocyte count and total bilirubin were significantly decreased (p < 0.05). Each patient showed an individual pattern of Hb F elevation. The increase in Hb F level was correlated with the haematological and biochemical parameters using the General Linear Model Programme of Statistical Analysis System. In general, the clinical presentation improved as Hb F level increased in each patient. In addition, the positive correlation with the haematological parameters and negative correlation with reticulocytes and total bilirubin confirmed the beneficial effect of elevated Hb F level on reducing red cell haemolysis. No correlation could be demonstrated between the pretreatment Hb F level and the increase in Hb F during the treatment period. Daily doses of HU with a single intravenous rHuEpo and iron supplementation elevate Hb F and Hb F cells in SCA patients. The Hb F level can be maintained high on HU therapy alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Granulocyte-Macrophage Colony-Stimulating Factor in Newly Diagnosed Adult Patients with Acute Lymphoblastic Leukemia Treated with Conventional Chemotherapy.

Twenty consecutive adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) were treated with conventional therapy consisting of daunorubicin, vincristine, prednisone and L-asparaginase in standard doses. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered at a single subcutaneous daily dose of 5 microgram per kilogram body weight for fourteen days starting on day 7 of chemotherapy. Twenty two adult patients with acute lymphoblastic leukemia and similar risk characteristics who received the same chemotherapeutic regimen without GM-CSF served as a historical control group. The complete remission rate and the rate of early mortality were similar in both groups of patients. Patients treated with GM-CSF showed significantly faster neutrophil recovery above 0.5 × 10(9)/L than the control patients (P < 0.005). The incidence of febrile episodes and the rate of documented infection were similar in the two groups of patients.

IgA antiphospholipid and adrenal insufficiency: Is there a link?

We present two females with antiphospholipid antibody (APA) syndrome who came with adrenal insufficiency (Addisons disease), recurrent abortions and extensive deep vein thrombosis (DVT). Both cases were positive for lupus anticoagulant (LA), global antiphospholipid test (APA), and IgG, IgA, IgM APA antibodies. Seventeen other cases with documented lupus anticoagulant and various clinical associations were tested for APA IgG, IgA, IgM. Only two were positive for IgA as well as IgG and IgM APA. Thirty volunteer blood donors (24 males and 6 females, aged 19-35 years) were taken as a control group. One person was moderately positive for LA and showed low positivity for IgG APA. These data suggest that the presence of IgA APA may signify a severe disease. Further studies are needed to confirm this observation.

Pregnancy outcome in women with antiphospholipid antibodies

SummaryThe association of antiphospholipid antibodies (APA) or lupus anticoagulant (LA) and recurrent fetal loss (RFL) is well established; however, the spectrum of pregnancy outcome in relation to various therapeutic approaches versus placebo is unknown. We studied 49 women with RFL, 14 with immune thrombocytopenia (ITP) 13 of whom without a history of RFL, and 32 controls (all in the first trimester of pregnancy) for the presence of APA. Tests for APA were positive in 15/49 women with RFL (30%), 6/14 ITP (43%) and 2/32 controls (6%). Treatment in the APA positive patients consisted of: no treatment for the 8 patients who had no history of RFL (Group A; all 34 previous pregnancies successful), aspirin alone (Group B, 5 patients; all 30 previous pregnancies unsuccessful), aspirin with prednisolone (Group C, 9 patients; 69/80 previous pregnancies unsuccessful), or aspirin, prednisolone and immunoglobulin G for resistant cases (Group D, 4 patients, previously in Group C). 10/11 (90.9%), 3/7 (43%), 7/13 (53.8%) and 4/7 (57.1%) pregnancies were successful in Group A, B, C and D, respectively. There was a total of 19/45 (42%) failures including 3 pregnancies in one patient who failed to respond to all forms of therapy.This open study with small subgroups of patients draws attention to a wide range of pregnancy outcome in women with APA and to the fact that APA may serve only as a marker for a wide range of pathological conditions with variable degrees of disease severity. More studies are, however, needed to explore the real mechanism of RFL in women with APA and RFL, especially those who are resistant to therapy.

Home treatment of haemarthrosis with recombinant activated factor VII in patients with haemophilia A or B and inhibitors: experience from developing countries

Home therapy for uncomplicated mild/moderate bleeding can decrease healthcare burden, promote self-esteem, reduce complications, and provide near-normal quality of life. To evaluate recombinant activated factor VII (rFVIIa) as home therapy for joint bleeds in Algeria, Morocco, Oman, Saudi Arabia, and United Arab Emirates. Twenty-seven patients aged more than 2 years with congenital haemophilia and inhibitors were monitored for up to 8 months after a first haemarthrosis episode treated with rFVIIa. Assessments were made by patients/caregivers with a standardized diary. The main measures included home-managed bleeds, haemostasis, and pain relief within 9 h after first injection. Additional analyses included convenience, time to pain resolution, and doses given within 48 h. Of 132 bleeds, 84 (63.6%) were managed at home. Of these, successful haemostasis (partial or complete) was achieved at 9 h in 87.8%, with pain relief for 84.0%. For all treatment settings, successful haemostasis at 9 h was achieved for 86.3% of bleeds, with pain relief achieved for 74.8% of bleeds. Higher initial dosing was associated with fewer injections. Median time to complete haemostasis was 48 h (spontaneous bleeds) and 24 h (traumatic bleeds). Median time to complete pain relief was 24 h for both bleed types. Satisfaction with treatment was high. No safety concerns were reported. Results from this observational study agree with previous data on the safety and efficacy of home treatment with rFVIIa and will help to increase awareness and aggregate experience, fostering confidence in home management of haemophilia patients with inhibitors in developing countries.

Unusual presentation of arsenic poisoning in a case of celiac disease.

Arsenic poisoning may occur from sources other than drinking water such as rice, seafood, or insecticides. Symptoms and signs can be insidious, non-specific, atypical, and easily overlooked. We present a 39-year-old woman with celiac disease who was on gluten-free diet for 8 years and presented with diarrhea, headache, insomnia, loss of appetite, abnormal taste, and impaired short-term memory and concentration, but with no skin lesions. Arsenic concentration in her 24-hour urine was 682.77 μg/g creatinine (normal <15). She responded very well to chelation therapy with dimercaptosuccinic acid given orally and recovered within 2 weeks. The suspected source of arsenic poisoning was rice, as drinking contaminated ground water is not known in Saudi Arabia and she had not taken seafood. Therefore, arsenic poisoning should be suspected based on the meticulous medical history in cases of patients with celiac disease whose main food is rice and who present with unusual symptoms.