Case Report: Pathogenic MYH9 c.5797delC Mutation in a Patient With Apparent Thrombocytopenia and Nephropathy

MYH9-related disease or disorder (MYH9-RD) is an autosomal dominant disease caused by mutations in the MYH9 gene. Mutations in this gene initially affect the hemic system, and other manifestations may evolve with age. Here, we report the case of a 46-year-old Chinese woman with MYH9-RD who was primarily misdiagnosed with idiopathic thrombocytopenia purpura. Exome sequencing of the patient, and the mother and son of the patient revealed a deletion mutation c.5797delC (p. R1933Efs*15) in exon 41 (encoding non-helical tailpiece, NHT) of the MYH9 gene, which consequently led to a frameshift mutation. To the best of our knowledge, this mutation has been reported in Italy once, while the substitution mutation c.5797 C>T is the most frequent mutation. Mutations that affect the NHT region cause thrombocytopenia throughout life; however, our patient presented with a more severe phenotype than previously reported, including thrombocytopenia, inclusion bodies in neutrophils, sensorineural hearing loss, nephropathy, and abnormal liver enzymes. Our goal in the current case is to prevent further progression of renal involvement and to identify other affected members in this family to provide early intervention. This case may raise awareness of MYH9-RD when diagnosing thrombocytopenia and improve our understanding of this condition.

Tuberculosis with Immune Thrombocytopenia an Unusual Association

Introduction Tuberculosis (TB) and is the leading infectious cause of death in adult's worldwide.TB can have a wide variety of presentations manifestation. Hematological manifestations of tuberculosis have different forms and one of the rare associated is TB with isolated thrombocytopenia. ITP is relatively common autoimmune bleeding disorder.. However, ITP is very rarely associated with TB with only a few cases reported. Isolated Thrombocytopenia in TB is multifactorial and could be explained by different mechanisms as follows Immune-mediated platelet destruction through antiplatelet antibodies as mycobacterium TB may share antibodies with platelets or platelet-associated immunoglobulin, Tuberculosis-induced hemophagocytosis, Defective platelet production due to bone marrow (BM) infiltration, Hypersplenism, intravascular coagulation, anti-tuberculous treatment (ATT) induced thrombocytopenia. Methodology We reviewed the literature using PubMed, google scholar and English language articles only. We have included all the reported cases of tuberculosis and immune thrombocytopenia if it is associations or initial presentations using the keyword: tuberculosis. Pulmonary tuberculosis, immune thrombocytopenia, Idiopathic thrombocytopenia purpura and we excluded drug induced thrombocytopenia. Our review identified forty-two cases in total, in our review Baseline and clinical characteristics are provided. Results Of the forty-two cases identified, more than one quarter of cases (n=12) were from India; the remainder of the reported cases from thirteen different countries. Gender was nearly equally distributed (males n= 21, females n=20, one case unknown); age ranged from 4 to 74 years. The most reported sites of TB as follows; lung (n=20), disseminated (n=8), lymph nodes (n=6), abdomen (n=4), mediastinum (n=2), spleen (n=1) and knee (n=1). Bone marrow aspiration and biopsy done in 27 cases, three of them (7%) found granuloma and 14 (32%) found to have normal to hyprecellular marrow with increased number of megakaryocytes. Of the forty-two cases, ITP was the first presentation of TB with or without typical TB symptoms and signs in more than three quarters of the cases (n=33), while ITP was discovered in TB patients in routine investigations without obvious bleeding symptoms or signs in only four cases. Hemorrhagic symptoms were reported in most of the cases (n=31), skin manifestations (petechiae/purpura/ecchymosis) being the most common (n=28). The therapeutic approach to TB-associated ITP showed significant heterogeneity with Anti tuberculous treatment and first- and/or second-line treatment for ITP given with or without platelets transfusion. Most of the cases (n=36) achieved full recovery with Anti-tuberculous treatment(ATT) and IVIG ± Steroids. Of the 42 cases, six cases were treated with blood and platelet transfusion for thrombocytopenia which did not normalize the platelet count as thrombocytopenia as expected as this is most likely an immune mediated phenomenon. Conclusion Unfortunately, there are no clear guidelines for management of TB-associated ITP and is anecdotal or observational at best. This highlights the importance of conducting prospective and standardized studies in the future. We found that Anti tuberculous treatment could have play pivotal role in management of ITP in TB Patients. Figure Disclosures No relevant conflicts of interest to declare.

Case Report: Rare comorbidity of celiac disease and Evans syndrome

Background: Celiac disease is an immune-mediated enteropathy due to permanent sensitivity to gluten in genetically predisposed individuals. Evans syndrome is an autoimmune disorder designated with simultaneous or successive development of autoimmune hemolytic anemia and immune thrombocytopenia and/or immune neutropenia in the absence of any cause. Case Report: We report a rare case of Celiac disease and Evans syndrome in a 20-year-old female who presented to us with generalized weakness and shortness of breath. Her examination finding included anemia, jaundice, and raised jugular venous pulse. Her abdominal exam revealed hepatosplenomegaly. Her laboratory values showed microcytic anemia, leukocytosis and thrombocytopenia. To rule out secondary causes of idiopathic thrombocytopenia purpura, we tested viral markers for Human immunodeficiency virus, Epstein bar virus, Cytomegalovirus and performed a Helicobacter pylori test, all of which were negative. We also ruled out idiopathic thrombocytopenia purpura associated with any thyroid disorder. For celiac disease, we took anti-tissue transgulataminase titers of IgA and IgG which confirmed the diagnosis of celiac disease. For the diagnosis of Evans syndrome, despite a negative serum coombs test initially, her bone marrow sample showed a positive Coombs test along with immune mediated hemolytic anemia and immune mediated thrombocytopenia. The patient was treated with prednisone which was tapered off and counseling was provided regarding a gluten free diet. Conclusion: Although rare, tests for Evans syndrome (and other coexisting autoimmune problems) should be performed in patients with celiac disease.

Idiopathic Thrombocytopenia Purpura Masking Hodgkin Disease: A Paraneoplastic Syndrome or Simply a Mere Association

We report a 74-year-old female who presented to the emergency department complaining of bruising and stroke-like symptoms. She underwent a negative stroke work-up but was found to have profoundly low platelets and splenomegaly on examination. An abdominal CT scan was ordered, showing pelvic lymphadenopathy. Lymphoma was suspected. However, subsequent bone marrow and lymph node biopsies showed no evidence of this. She was treated for immune thrombocytopenia purpura (ITP) to no avail while a lymphoma work-up continued. Months later, a third and final lymph node biopsy yielded evidence of Hodgkin disease (HD) and she began treatment shortly thereafter. She is currently undergoing standard treatment for this malignancy and her platelet counts have normalized. The case not only outlines the importance of the physician’s gestalt in arriving at the proper diagnosis, but it also posits the thought that perhaps ITP should be considered a paraneoplastic syndrome of HD.

Long Term Outcomes for Patients with Cyclic Neutropenia Treated with Granulocyte Colony-Stimulating Factor (G-CSF)

Cyclic neutropenia (CyN) is a rare hematological condition with neutrophil counts decreasing to <0.2 x 109/L, usually at 21 day intervals, accompanied by fever, mouth ulcers and the risk of severe sepsis during the neutropenic periods. Twenty-six years ago we reported results of treating six patients with CyN on G-CSF (N Engl J Med. 1989;320: 1306-1311). We have now followed these patients and many other CyN on G-CSF for up to 28 years through the Severe Chronic Neutropenia International Registry (SCNIR). The original six patients (2 male, 4 female, ages 8.8 to 65) are all living, now ages 36 to 92 years. All of the original six had documented fever and recurring infections prior to treatment (i.e. mouth ulcers, gingivitis, lymphadenopathy, cellulitis, abscesses, pharyngitis, otitis, and pneumonia). Five were found to have mutations in ELANE after the discovery of mutations in this gene as the cause for CyN. The sixth patient, in retrospect, probably more appropriately should have be given the diagnosis of severe idiopathic neutropenia, is now age 92, off G-CSF and residing at home with skilled nursing care. The other five have maintained good health on G-CSF treatment and are now employed as teachers, working in a business, or retired. None have developed notable infections, hematological or other sequelae except for one patient with decreased bone density and one patient with idiopathic thrombocytopenia purpura (ITP) responding to splenectomy. In aggregate these six patients have received approximately 6.6 grams of G-CSF over 143 patient-years (median dose of G-CSF per patient per year is 0.035 gm, range 0.018 to 0.075 gm, treatment period: 7-28 years). Our broader experience with 308 patients with the diagnosis of CyN based on serial blood counts and/or genotyping and treated with G-CSF is similar to these original six patients. However, we are aware of at least 40 cases of severe sepsis and 17 deaths in patients with CyN not on G-CSF. We are not aware of any such severe infections in CyN patients consistently receiving G-CSF (i.e. at least two or three times per week). We have recorded one case on chronic myeloid leukemia in a CyN patient never on G-CSF. For patients receiving G-CSF we have recorded one case of non-Hodgkin's lymphoma, one case of AML in patient with probable CyN having 2 ELANE mutations and a secondary CSF3R mutation, and one case of AML after chronic immunosuppressive therapy with cyclophosphamide. Conclusion: Observations in 308 patients for 2993 years demonstrate that G-CSF is a very beneficial treatment for patients with CyN. There is good evidence that this treatment prevents severe infections and death from infections and there is a very low risk myeloid malignancies, and specifically conversion to MDS or AML. Disclosures Dale: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Boxer:Amgen: Equity Ownership.