Mahidol Scoring for Assessing Various Grades of ß Thalassemia Intermedia.

OBJECTIVE: To determine the effectiveness of Mahidol Scoring for assessing various grades of ß thalassemia intermedia. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Fatima Memorial Hospital, Shadman, Lahore, from August 2016 to August 2017. METHODOLOGY: A total of 150 patients, both inpatient and outpatient diagnosed as thalassaemia intermedia fulfilling inclusion criteria, were enrolled, interviewed and examined after an informed consent. All patients were assessed by using Mahidol Scoring system. Their scores were documented on a predesigned evaluation porforma. Patients were labelled as mild, moderate or severe diseased. RESULTS: In a total of 150 patients, 88 (58.7%) were males and 62 (41.3%) were females. Using Mahidol Scoring, 88 (58.7%) were labelled as mild, 53 (35.3%) as moderate and 9 (6%) as severe diseased. Patient who were labelled as mild diseased according to Mahidol Scoring, had no blood transfusions and showed good response to hydroxyurea. Patients with moderate score, were infrequently transfused and showed variable response to hydroxyurea. Patients in severe group received first transfusion at an early age, maintained lower Hb levels, showed growth retardation, splenomegaly, and had poor response to hydroxyurea. CONCLUSION: Mahidol Scoring system is an easy, safe and effective way for classification of thalassaemia Intermedia severity. The grades according to Mahidol Scoring system will aid in the management of patients as the score can be quickly calculated, and can assist the clinician in an initial evaluation for disease severity in patients of thalassaemia intermedia.

Autoimmune lymphoproliferative syndrome with neonatal onset.

We describe 2 cases of autoimmune lymphoproliferative syndrome (ALPS), which is a rare disorder of auto-immunity, chronic persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly and hyper gamma globulinemia (1gG, 1gA). Both cases presented in neonatal period which is a rare age of presentation in this disease. A 20 days old female neonate presented with respiratory symptoms which rapidly progressed needing ventilatory support. There was hepatomegaly and no auscultatory findings in the chest. Serial CBCs (complete blood counts) showed persistent leucocytosis with predominant lymphocytosis. Her chest X-ray showed left sided consolidation which responded poorly to antibiotics. Her prompt clinical response to steroids raised the suspicion of autoimmunity and the diagnosis was established after a negative bone marrow examination for leukemia and a positive result for ALPS on flow cytometry. The second case presented with anemia, thrombocytopenia starting in neonatal period followed by persistent lymphadenopathy, hepatosplenomegaly and recurrent infections which responded poorly to antibiotics. Diagnosis was delayed due to low index of suspicion, and finally achieved with multiple radiological studies, histopathology and flow cytometry.

Congenital amegakaryocytic thrombocytopenic purpura (CAMT).

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL) despite high levels of serum TPO. Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. The primary treatment for CAMT is bone marrow transplantation. This report describes a newborn girl who presented to us with symptoms of sepsis but septic profile came negative except thrombocytopenia. Bone marrow biopsy was done for thrombocytopenia which revealed amegakaryocytic thrombocytopenia. She was given prednisolone.

Frequency of beta-thalassemia trait in families of thalassemia major patients, Lahore.

BACKGROUND: Thalassemia major is one of the most common genetic disorders in Pakistan and over five thousand new patients are added in the pool annually. This familial disease has both medical and social implications, and therefore there is a need to assess the magnitude of beta-Thalassemia trait amongst family members of Thalassemia major patients. METHODS: This cross-sectional descriptive study enrolled 674 blood samples from first degree relatives of registered patients of Thalassemia major at Sir Ganga Ram Hospital, Lahore. Peripheral blood smears were studied for abnormal morphology findings of microcytosis, hypochromia, poikilocytosis (tear drops, target cells) and Erythrocyte indices (haemoglobin, RBCs, mean corpuscular haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin concentration) and Hb electrophoretic (HbA, HbA2, & HbF). RESULTS: Hb electrophoresis showed 61% of the study subjects had haemoglobinopathies. Frequency of beta-Thalassemia trait was highest followed by beta-Thalassemia major, HbE trait, HbD Punjab and Hb intermedia. CONCLUSION: Findings strongly suggest screening for beta-Thalassemia trait in families of Thalassemia major patients.

An SCN9A channelopathy causes congenital inability to experience pain.

The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit.