Case Report: A Case of Leukocyte Adhesion Deficiency, Type III Presenting With Impaired Platelet Function, Lymphocytosis and Granulocytosis.

Fermitin family homolog 3 (FERMT3), alternatively kindlin-3 (KIND3), is an integrin binding protein (of 667 residues) encoded by the FERMT3 gene. The molecule is essential for activating integrin αIIbß3 (the fibrinogen receptor) on platelets and for the integrin-mediated hematopoietic cell (including platelets, T lymphocytes, B lymphocytes, and granulocytes) adhesion. Its defects are associated with impaired primary hemostasis, described as "Glanzmann's thrombasthenia (MIM#273800)-like bleeding problem." The defects are also associated with infections, designated as "LAD1 (leukocyte adhesion deficiency, type I; MIM#116920)-like immune deficiency." The entity that joins the impaired primary hemostasis with the leukocyte malfunction has been termed "leukocyte adhesion deficiency, type III" (LAD3, autosomal recessive, MIM#612840), representing a defective activation of the integrins ß1, ß2, and ß3 on leukocytes and platelets. Here, we report a male toddler with novel compound heterozygous variants, NM_178443.2(FERMT3):c.1800G>A, p.Trp600* (a non-sense variant) and NM_178443.2(FERMT3):c.2001del p.*668Glufs*106 (a non-stop variant). His umbilical cord separated at about 3 weeks of age. A skin rash (mainly petechiae and purpura) and recurrent episodes of severe epistaxis required blood transfusions in early infancy. His hemostatic work-up was remarkable for a normal platelet count, but abnormal platelet function screen with markedly prolonged collagen-epinephrine and collagen-ADP closure times. The impaired platelet function was associated with reduced platelet aggregation with all agonists. The expression of platelet receptors was normal. Other remarkable findings were persistent lymphocytosis and granulocytosis, representing defects in diapedesis due to the integrin dysfunction. The natural history of his condition, structure and sequence analysis of the variations, and comparison with other LAD3 cases reported in the literature are presented.

Red Blood Cell Alloimmunization in Multitransfused Pediatric Population in a Tertiary Care Hospital.

OBJECTIVES: To estimate the prevalence and specificity pattern of red blood cell (RBC) alloimmunization among pediatric multitransfused patients, and to identify the factors associated with alloimmunization. METHODS: This was a descriptive cross-sectional study conducted among mutitransfused pediatric patients over a period of two years. The relevant clinical details of patients were collected, and RBC antibody screening was done. Samples with positive antibody screen were subjected to antibody identification. Patient factors were analysed to find any significant relation to the development of RBC alloimmunization. RESULTS: Alloantibodies were obtained in 4 (6.35%) of the total 63 patients, and autoantibody in 1 (1.59%). The specificities of alloantibodies identified were all against Rh antigens-one each of anti E, anti c, anti Cw and anti D + anti C. A significant association was seen between development of alloimmunization and first transfusion at more than 2 y of age. CONCLUSIONS: RBC alloimmunization against Rhesus (Rh) antigens is a significant problem for multitransfused children in our population. Extended RBC phenotyping at least for antigens of the Rh system and provision of antigen matched RBCs may be an option for such children, where ongoing transfusion requirement is anticipated.

Lineage shift in Indian strains of Dengue virus serotype-3 (Genotype III), evidenced by detection of lineage IV strains in clinical cases from Kerala.

BACKGROUND: Local epidemiology of Dengue is defined by the genetic diversity of the circulating Dengue virus (DENV) strains. This important information is not available for the virus strains from most parts of the Indian subcontinent. The present study focused on the genetic diversity of the serotype 3 DENV strains (DENV-3) from India. RESULTS: A total of 22 DENV-3 strains identified by reverse-transcription PCR analysis of serum samples from 709 patients were studied. These samples were collected over a period of 4 years (2008-2011) from dengue fever suspected patients from Kerala, a dengue endemic state in South India. Comparison of a 1740bp nucleotide sequence of the viral Capsid-Pre-membrane-Envelope coding region of our strains and previously reported DENV-3 strains from India, South Asia and South America revealed non-synonymous substitutions that were genotype III-specific as well as sporadic. Evidence of positive selection was detected in the I81 amino acid residue of the envelope protein. Out of the 22 samples, three had I81A and 18 had I81V substitutions. In the phylogenetic analysis by maximum likelihood method the strains from Kerala clustered in two different lineages (lineage III and IV) within genotype III clade of DENV-3 strains. The ten strains that belonged to lineage IV had a signature amino acid substitution T219A in the envelope protein. Interestingly, all these strains were found to be closely related to a Singapore strain GU370053 isolated in 2007. CONCLUSIONS: Our study identifies for the first time the presence of lineage IV strains in the Indian subcontinent. Results indicate the possibility of a recent exotic introduction and also a shift from the existing lineage III strains to lineage IV. Lineage shifts in DENV-3 strains have been attributed to dramatic increase in disease severity in many parts of the world. Hence the present observation could be significant in terms of the clinical severity of future dengue cases in the region.

Iron deficiency as a risk factor for simple febrile seizures--a case control study.

OBJECTIVE: To study the role of iron deficiency as a risk factor for simple febrile seizures. DESIGN: Case control study. SETTING: Pediatric department of a tertiary care teaching hospital. PARTICIPANTS: 154 cases and 154 controls were included in the study. Consecutive cases and concurrent controls were selected. Cases were children of age group 6 months to 3 years presenting with simple febrile seizures. Controls were children of same age group presenting with short febrile illness but without any seizures. METHODS: After informed consent, detailed history was taken and clinical examination done in both cases and controls and blood investigations were done to diagnose iron-deficiency in both cases and controls. Iron deficiency was diagnosed as per WHO criteria (hemoglobin value <11 g%, red cell distribution width of >15% and serum ferritin value <12 ng/mL). Other explanatory variables, which can be the potential confounders were also included in the study and considered for analysis. RESULTS: Highly significant association was found between iron deficiency and simple febrile seizures in both univariate and multivariate analysis. Crude odds ratio was 5.34 (CI 3.27- 8.73, P<0.001) and adjusted odds ratio in the logistic regression analysis was 4.5 (CI 2.69- 7.53, P <0.001). CONCLUSIONS: Iron deficiency is a significant risk factor for simple febrile seizures in children of age group 6 months to 3 years.

Acute encephalopathy with a lesion of the splenium of the corpus callosum--a report of two cases.

We report two cases of encephalopathy following a short febrile illness. Case one was a five year old child whose magnetic resonance imaging (MRI) of the brain showed a reversible discrete lesion in the splenium of the corpus callosum (SCC) and a ten year old boy who had extensive hyperintensity of the SCC. As these children have presented while there was an outbreak of influenza in our locality and since the second child tested positive for H1N1 antigen on PCR test, we feel that as previous authors have pointed out, these cases are cases of possible influenza encephalopathy. This awareness needs to be disseminated as this specific MRI finding should prompt one to test for H1N1 antigen and offer specific antiviral agent. Case one showed signs that support the existence of a splenial syndrome.

Diagnostic re-evaluation of children with congenital hypothyroidism.

OBJECTIVES: To investigate the causes of congenital hypothyroidism in children more than 3 years of age and to document the frequency of transient vs permanent hypothyroidism. DESIGN: Hospital based observational study. SETTING: Pediatric endocrine clinic of a medical college. PATIENTS: Children over 3 years of age, on treatment for congenital hypothyroidism. INTERVENTION: Thyroid function test (TFT) and thyroid ultrasound was done. Children with agenesis or hemiagenesis in thyroid ultrasound were identified. In children with normal or equivocal thyroid ultrasound, thyroxine was stopped and followed. Children with abnormal TFT on follow up had thyroid scintigraphy with or without potassium perchlorate discharge, after which, thyroid hormone supplement was restarted. Children who remained euthyroid on follow up were labeled as having transient hypothyroidism. MAIN OUTCOME MEASURE: Proportion of children with transient hypothyroidism. RESULTS: Among 36 children studied (20 boys and 16 girls), eighteen (50%) had transient hypothyroidism and fifteen (41.7%) had thyroid agenesis. There was one with hemiagenesis, one with ectopic thyroid and another with dyshormonogenesis (2.8% each). Initial TSH level at the time of diagnosis was higher in permanent hypothyroidism as compared with transient group (83.0 ± 31.6 vs 47.0 ± 33.1 mIU/mL; P= 0.002). CONCLUSIONS: Thyroid hormone supplementation could be discontinued in 50% of children diagnosed with congenital hypothyroidism.

The newborn with seizures -- a follow-up study.

OBJECTIVE: To determine the sequelae of neonatal seizures in a cohort of newborns, recruited over a six month period. DESIGN: Prospective hospital based study. SETTING: The neonatal intensive care unit (NICU) of a tertiary care hospital. PARTICIPANTS: 135 babies were recruited of whom 10 died and 25 were lost to follow up. METHODS: The cases were followed up over four months. RESULTS: 68% of the babies followed up were normal; 32% had an abnormal neurological outcome. Seven (7%) developed post-neonatal epilepsy. Hypocalcemia was significantly associated with mortality (OR: 21.9; 95% CI: 1.2-391.2). No risk factors could be identified for post neonatal epilepsy. Presence of spike waves in the EEG was significantly related to abnormal neurological outcome (OR: 3.5; 95% C.I. 1.2-10.8). CONCLUSIONS: Majority of neonates with seizures have a normal outcome with no developmental delay or neurological deficit. Predominantly spike waves in the EEG is predictive of abnormal neurological outcome.