Infections in Hb SD Disease

Infections in Hb SD DiseaseCase ReportHBSD Disease, a compound heterozygote condition presentation with strokeDr. Hasnain Afzal 1 Dr. Syed Farrukh Umair 2AbstractHaemoglobin SD S/D is a rare compound heterozygous Haemoglobinopathy which presents as severe disease similar to homozygous reap hook cell anemia(1). The forbearing being reported is a 8 yr old girl, Kiran who is a resident of Larkana, presented with complains of fever and headache for 15 days which progressed to conclude tonic clonic seizures and acute loss of consciousness while being treated in Larkana. later the child was stabilized, a thorough history, physical examination was done initial laboratory tests, lumbar puncture, and MRI were performed. Treatment was started on the lines of acute meningoencephalitis on clinical suspicion. On peripheral blood film, reaping hook shaped cells, objective lens cells, poikilocytosis, anisocytosis were noted and Hb Electrophoresis was sent which showed compound heterozygous s tate for Hb S/ Hb D. The lumbar puncture was minus for CSF infection and an alternate diagnosis was soughtIntroductionThe adult haemoglobin HbA molecule consists of cardinal chains coded by 4 genes on chromosome 16 and two of import chains coded by 2 genes in the gene cluster on chromosome 11(2). reaping hook Hemoglobulin Hb S is a beta chain miscellaneous which occurs when valine is substituted for glutamic acid on the surface of the Hb S molecule in the sixth codon of the beta globin chain whereas the most common subtype of HbD i.e HbD Punjab also know as Haemoglobulin D Los Angeles (after the city where it was first discovered) is also a beta chain variant caused by a glutamic acid to glutamine substitution at codon 121 of the beta globin gene. HbS is associated with a number of compound heterozygous syndromes with other mutant beta globin which include haemoglobin SC disease, Sickle beta+thalassemia, Sickle beta0thalassemia, Sickle alpha thalassemia, Sickle transmissib le persistence of HbF (sickle HPFH), Other less common sickle cell syndrome variants (eg, delta beta0thalassemia, Hb Lepore, HbD, HbO Arab, HbE). HbSD presents as mild to moderate hemolytic anemia unlike HbD homogyzous and simple hetrozygotes which are usually asymptomatic.(3)DiscussionA study done on abnormal hemoglobin variants among the major ethnic groups of Karachi in 2002 showed that 60% had iron-deficiency anemia and 40% had hemolytic anemia, of which 20.6 % was due to thalassemia major, 13% thalassemia trait, 5.1% sickle cell disease, 0.76% hemoglobin D Punjab (HbD Punjab), 0.32% hemoglobin C (HbC), and 0.22% hereditary persistence of fetal hemoglobin (HPFH) (4).Hb S is the most common Hb variant, its clinical offcome is severe in homozygous or when associated with other hemoglobinopathies, much(prenominal) as beta-thalassemia, Hb C or Hb D. (5). A number of studies have been done on Hb S and Hb C tho Hb D is still poorly studied especially in Pakistan. Hemoglobin D has s everal varients such as HbD Punjab (Los Angeles), Hb D Iran, Hb D Ibadan and Hb D Bushman but the most common variant is HbD-Los Angeles (also called HbD-Punjab). High performance liquid chromatography (HPLC) can be used to separate hemoglobin polypeptide chains in the laboratory. High performance liquid chromatography (HPLC) pursues ion exchange method to identify and exchange various fractions of Hb.Hb D can be also terrific from Hb S by acid electrophoresis or isoelectric focusing (IEF) (separation according to isoelectric points). On alkali electrophoresis (cellulose acetate) Hb D Punjab migrates slower than Hb A which is similar to HbS but its migration under acid electrophoresis (agarose gel) is similar to Hb A (6) In HbSD disease, HbD does not take part in the sickling process, as patients homozygous for HbD do not sickle but mild hemolytic anemia, mild to moderate splenomegaly may occur (7,8). Studies has indicated that although HbD itself does not polymerize, it increase s the hydrophobic interaction amid Hb S molecules and facilitates the polymerization of HbS thus enhancing the severity of the disease. (9) HbD heterozygotes with normal HbA have no clinical or hematologic alterations. (6) Table 1.1 Hb Electrophoresis interrogatory Done on high performance liquid chromatography (HPLC)HaemoglobinTest PercentageNormal PercentageHaemoglobin A20.7%(98-100)Haemoglobin A22.6%(1.5-3.5)Haemoglobin F13%(1-2) Haemoglobin D37.9%(0.0-0.0)Haemoglobin S25.8%(0.0-0.0)Interpretation A+F+D+S+A2Case Report8 yr old, 16 kg, Kiran resident of Larkana district, presented to us on 7th April, 2015 with acute loss of consciousness and recurrent episodes of seizures for 3 days. Patients father reported that she was in a usual state of health 15 days back when she real high grade intermittent fever and constant severe headache associated nausea, throw up and neck stiffness. She was taken to a primary care hospital in Larkana and treated on the lines of viral/bacterial me ningoencephalitis. During her hospital stay in Larkana she developed recurrent episodes of generalized tonic clonic seizures which were controlled by multiple antiepileptic agents. First Lumbar pucture was done on 31ST March, 2015 and CSF DR showed 21mg/dl Protein, 68 mg/dl Glucose, CSF TLC 17 and 2-3 RBC/HPF. CT was done on 31st March, 2015 showed generalized brain edema. Upon arrival in ICU Patel Hospital the patient was in a comatose condition with GCS 5/10, bilateral upgoing planters and flexor response to pain(decorticate) Patient was febrile 103F, other vitals were BP 130/90, Pulse 100, RR 28. After the child was stabilized, a thorough history, physical examination was done initial laboratory tests, lumbar puncture, and MRI were performed. CBC showed normocytic anemia and peripheral film showed target cells, sickle cells, anisocystosis, poikilocytosis, polychromasia diamorphic picture. Hb Electrophoresis was sent on hematologist advice. Patient was started on mannitol to decr ease intracranial pressure and multiple antiepileptic agents for seizure prevention. ATT, bacterial and viral meningitis cover was given and CSF DR was sent on 9th April, 2015 which showed 27 mg/dl Protein, 71 mg/dl Glucose, Chloride 123 mg/dl, TLC 04 and 17 RBC/HPF. CSF fluid gram stain, culture were initially negative. AFB Culture report to follow in 6 weeks. MRI done on 8th April, 2015 showed widespread abnormal signal intensity area involving bilateral frontal and parietal lobes. Few focal hyperintense signals were identified on bilateral occipital region which may represent areas of ischemic infarction. An alternate diagnosis such as cerebral ischemia due to small infarcts/ vasculitis involving bilateral frontal and parietal lobes was sought lower-ranking to Hb SD disease. Patient had significant improvement in GCS 10/15 with spontaneous eye opening, withdrawal on pain and few incomprehensible sounds and was shifted out of the ICU due to financial constraints.Graph 1.1 High P erformance Liquid ChromatographyConclusionThe case demonstrates increase susceptibility to infections in Hb SD disease. Studies are seldom on Hb D in Pakistan. Genetic counceling is of pivotal role in hereditary hemoglobinopathies and hospitals should consider it as an important management strategy and employ in hospital genetic counceling facilities. Hydroxyurea used to increase Hb F levels in Homozygous Sickle Cell Disease Hb SS disease has shown cleverness by reducing the complications, frequency of transfusions and hospitalization but its role in Hb SD Punjab is not well established. A recent study in India showed reducing in incidence of vaso-occlution and frequency blood transfusions in Hb SD Punjab disease which is encouraging and more studies should be done on the management of Hb SC compound heterozygous disease. (10)ReferencesRahimah A, Syahira Lazira O, Siti Hida HM, Faidatul Syazlin AH, Nur Aisyah A, Nik Hafidzah NM, Zubaidah Z. Haemoglobin sickle d punjab a case repor t. Med J Malaysia. 2014 Feb69(1)42-3.Birol G, Abdullah C, Cagatay U4, Sule MY, Ferda TT, Sevcan TB. -Globin chain abnormalities with coexisting -thalassemia mutations. Arch Med Sci 2012 8, 4 644-649.El-Kalla S, Mathews A R. HbD Punjab in the linked Arab Emirates. Hemoglobin 199721369-75.Ghani R,Manji MA,Ahmed N. Hemoglobinopathies among five major ethnic groups in Karachi, Pakistan. Southeast Asian J Trop Med Public Health.2002 Dec33(4)855-61.Thom CS, Dickson CF, Gell DA, Weiss MJ. Hemoglobin variants biochemical properties and clinical correlates. 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