An amiss complement pathway can cause atypical hemolytic uremic syndrome (aHUS) with microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. An observational study to understand complement abnormalities and outcome among pediatric aHUS in absence of targeted therapy was done. We enrolled 35 children from July 2017 to December 2018. Besides recording clinical details, hematological and renal parameters were assessed. Complement analysis included a one-time evaluation of C3, C4, anti-factor H antibody (VIDITEST human ELISA kit), factor H, I, B (Sinogeneclon ltd.) and CD46/membrane co-factor protein (MCP) (flow cytometry). SPSS version 23 (Chicago, IL) was used for analysis. Median age was 49 months (sex ratio of 1.7:1). Hypertension was noted in 74.2%(26) and central nervous system involvement in 34.3%(12). At admission, mean hemoglobin was 6.7±1.8 g/dL, median platelet count was 78x109 cells/L(38,101) and median eGFR was 11.91ml/min/1.73m2(6.5, 21.3). C3 was low in 57% (20), while 25.7% (9) had low C4 levels. Anti-factor H antibody was positive in 44% (15). Low expression of MCP in leucocytes was seen in 26.7% (8). Further, 3 had low factor H and high factor B respectively, while 2 had low factor I levels. Plasma-therapy was initiated in 65.7%. Remission was noted in 48.5% (17), 31.4% (11) died and others discontinued treatment. Though anti-factor H antibody is the most common followed closely by low MCP expression, abnormal levels of different complement proteins were observed. Outcome was dismal without eculizumab. We recommend comprehensive complement analysis in pediatric aHUS. Development and availability of targeted therapy remains unquestionable.

A document by Sanghamitra Machhua. Click on the document to view its contents.

Title of manuscript : Forme fruste of scleroderma and autoimmune hearing loss in a young adult with X linked agammaglobulinemia Authors-Munish Arora, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaPallavi Nadig, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaSanchi Chawla, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaSaniya Sharma, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaAmit Rawat, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaRamandeep S. Virk, Department of Otorhinolaryngology, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaAnkur Kumar Jindal, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, India.

Background: There is paucity of literature on long term follow-up of patients with Hereditary angioedema (HAE) from developing countries. Objective: This study was carried out to analyse the clinical manifestations, laboratory features and genetic profile of 32 patients (21 male and 11 female) from 23 families diagnosed with HAE between January 1996 and December 2019. Methods: Data were retrieved from medical records of the Paediatric Immunodeficiency Clinic, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Results: Median age at onset of symptoms was 6.25 years (range 1–25 years) and median age at diagnosis was 12 years (range 2-43 years). Serum complement C4 level was decreased in all patients. All patients had low C1- esterase inhibitor (C1-INH) quantitative level (type 1 HAE). SERPING1 gene sequencing could be carried out in 20 families. Of these, 11 were identified to have a pathogenic disease-causing variant in the SERPING1 gene. While 2 of these families had a previously reported mutation, remaining 9 families had novel pathogenic variants in SERPING1 gene. Because of non-availability of C1-INH therapy in India, all patients were given long term prophylaxis (attenuated androgens or tranexamic acid or a combination of the 2). Life-threatening episodes of laryngeal oedema were managed with fresh frozen plasma infusions. Only one disease related mortality was reported in the entire cohort. Conclusions: We report largest single centre cohort of patients with HAE from India. Attenuated androgens, fibrinolytic agents and fresh frozen plasma may be effectively used for management of HAE in resource limited settings.

Title PageManuscript type: Letter to editorTitle: Bridging diagnosis of a rare hematological disorder through genetic testing in a young girl with persistent panleukopeniaRunning title: Young girl with persistent panleukopenia

Myriad faces of X-linked agammaglobulinemia in a young boyAuthors: Murugan Sudhakar1, Manpreet Arora1, Lesa Dawman1, Dharmagat Bhattarai1, Pratap Kumar Patra1, Ankur Kumar Jindal1, Ritambhra Nada2, Amit Rawat1, Karalanglin Tiewsoh1