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P274 Novel dedicator of cytokinesis 8 (DOCK8) mutation in child with eczema and recurrent skin abscesses
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 119 (2017) S17eS96
P271 EXPERIENCE WITH TWO PATIENTS WITH ACTIVATED PI3K DELTA SYNDROME: CASE REPORTS A. Stoner*, J. Kennedy, A. Berlinski, S. Jones, A. Scurlock, Little Rock, AR. Introduction: Activated Phosphoinositide-3 Kinase (PI3k) delta syndrome (APDS) is a combined immunodeficiency caused by gain of function mutations in PIK3 protein or receptor. We present two patients with APDS, one protein (APDS1) and one receptor mutation (APDS2). Methods: Chart reviews detailed both patients’ clinical presentation and course, pulmonary function tests (PFTs), bronchoscopies, and immunologic/genetic testing. Results: Patient 1 is a male who presented at age 3 years with frequent infections and combined immunodeficiency. At 9yo, he developed bowel obstruction secondary to abdominal lymphoproliferation. PET scans of the lungs showed right sided consolidative mass and increased peri-tracheal lymphadenopathy. PFTs showed FVC 100%, FEV1 105%, and FEV1/FVC 96. Bronchoscopy revealed nodularity of main stem and segmental bronchi. Genetic testing showed a heterozygous missense mutation of APDS-1 (APDS1). He started sirolimus with improvement in clinical symptoms and reduced lymphoproliferation observed on bronchoscopy. Patient 2 is a female who presented at age 3 years with recurrent infections, increased IgM and antibody deficiency. At age 8 years, she developed upper airway lymphoproliferation, requiring numerous tonsillar debulking procedures. Bronchoscopy revealed nodularity and significant narrowing of left mainstem bronchus. PFTs showed FVC 66%, FEV1 68% and FEV1/FVC 93, a moderate restrictive pattern. Genetic testing showed a de novo autosomal dominant heterozygous variant in PIK3R1 gene (APDS2). She started sirolimus, and bronchoscopy improved, but PFTs remained unchanged. Conclusion: Both APDS patients presented with immune deficiency and lymphoproliferation; however, our patient with APDS2 resulting from mutation in PIK3R1 had a more severe clinical course requiring aggressive surgical management as well as immunomodulatory therapy.
vitro activation, confirming the diagnosis of XHIGM. His cutaneous warts remain recalcitrant. Conclusion: Susceptibility to viral infections is not a hallmark of XHIGM. This case of severe cutaneous warts represents an unusual presentation for CD40L deficiency.
P273 A CASE OF AGAMMAGLOBULINEMIA ATTRIBUTED TO HETEROZYGOUS, DOMINANT-NEGATIVE MUTATION IN TRANSCRIPTION FACTOR E47 E. Feuille*, B. Boisson, Y. Itan, J. Casanova, C. Cunningham-Rundles, New York, NY. Background: The majority of patients with early-onset infections and agammaglobulinemia have recessive mutations that impair downstream signaling through the B cell- and pre-B cell-receptors. One previous study identified 4 unrelated agammaglobulinemic patients with a dominant-negative mutation in the TCF3 gene encoding transcription factor E47, resulting in mutant protein E555K. Here we describe the case of a patient found to have this same mutation. Case Presentation: The patient initially presented at 4 years of age with chronic sinusitis and recurrent otitis. His immunoglobulins were undetectable; testing for BTK mutation was negative. After starting on monthly infusions of immunoglobulin, his symptoms improved. Other than occasional diarrhea and sinus infections 3 to 4 times per year, he has had an uncomplicated course until his current age of 26 years. His parents, brother, and three sisters are all without evidence of immunodeficiency. B cell count on most recent lymphocyte screen was 1/cu mm. On whole-exome sequencing, he was found to have heterozygous missense mutation in the TCF3 gene for E47, with resultant mutant protein E555K. Conclusions: This case report provides further evidence that E47 is critical in B cell development, and that a heterozygous mutation in E47 is associated with autosomal dominant agammaglobulinemia. With this patient sharing the same mutation with 4 previously described cases, this case supports the assertion that a mutational “hot-spot” exists in the E47 gene. Identification of this mutation may have prognostic value and will guide genetic counseling.
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P274
DISSEMINATED CUTANEOUS WARTS IN X-LINKED HYPER-IGM SYNDROME: A CASE REPORT H. Ho*, C. Cunningham-Rundles, New York, NY.
NOVEL DEDICATOR OF CYTOKINESIS 8 (DOCK8) MUTATION IN CHILD WITH ECZEMA AND RECURRENT SKIN ABSCESSES O. Waqar*1, B. Kaplan2, 1. Dix Hills, NY; 2. Great Neck, NY.
Introduction: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency caused by mutations in the CD40Ligand (CD40L) gene, leading to defective immunoglobulin class-switch recombination and impaired T-cell activation. Well-known manifestations of the syndrome include recurrent sinopulmonary infections, gastrointestinal complications, and neuroendocrine tumors. Cutaneous warts have rarely been reported in XHIGM. Case Presentation: We report a case of chronic disseminated warts in a 49-year-old male with hypogammaglobulinemia. The patient was diagnosed with primary antibody deficiency (IgG: 107mg/dL, IgA: 70mg/dL, and IgM: 70mg/dL) at age 3 in the setting of frequent sinopulmonary infections. There was no family history of immunodeficiency. He developed cutaneous warts at age 5, with increased severity since age 12. Physical exam was remarkable for warts covering his trunk and extremities, as well as coalesced warts forming thick hyperkeratotic plaques on his hands and feet. He failed multiple treatments including peg-interferon alpha and intralesional candida immunotherapy. His history was notable for HPV-negative urothelial carcinoma at age 42 and presumed diagnosis of common variable immunodeficiency since childhood. Due to his unusual presentation, whole exome sequencing was sent and it revealed a pSer214 frameshift mutation in his CD40L gene and carrier status in his mother. Flow cytometry analysis demonstrated a lack of CD40L expression on the surface of CD4+ T-cells upon in
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Introduction: DOCK8 deficiency is an autosomal recessive combined immunodeficiency syndrome associated with recurrent infections, eczema and other atopic diseases. The infections are usually viral, bacterial and fungal resulting in predominantly cutaneous and sinopulmonary manifestations. Homozygous or compound heterozygous deletions or mutations in the DOCK8 gene (9p24) lead to abnormal cytoskeletal organization and impaired function of dendritic cells and lymphocytes. Case Presentation: We present a three-year-old male with moderate-severe eczema, asthma, peanut and egg allergy who suffered from recurrent skin abscesses. Other infectious history included otitis media. There was no history of pneumonia or other severe infections. Skin abscesses responded to oral antibiotics, but recurred shortly after completing extended courses of treatment. The skin abscesses did not recur while the patient was on prophylactic antibiotics. Abscess cultures grew Enterococcus faecalis and Staphylococcus aureus. Laboratory results including quantitative immunoglobulins, specific antibody titers, myeloperoxidase staining, neutrophil oxidative burst and complement were within normal limits. IgE was elevated (6740 IU/mL) and there was a mild eosinophilia (1200 eosinophils/microL). T and B cell enumeration was essentially unremarkable with mild elevations in CD3 and CD4. DOCK8 genetic sequencing by GeneDx revealed a heterozygous
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Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 119 (2017) S17eS96
missense mutation in exon 17 (c.1979 C>A, amino acid change p.Ala660Asp). Conclusion: The need for long term antibiotics to control recurrent skin abscesses should raise suspicion for an underlying immunodeficiency. DOCK8 deficiency should be considered in patients with severe eczema and recurrent abscesses despite appropriate antibiotics. The p.Ala660Asp missense mutation in the DOCK8 gene may represent a novel pathogenic variant.
P275 REFRACTORY HYPEREOSINOPHILIA MANIFESTING AS NODULAR SCLEROSIS CLASSICAL HODGKIN LYMPHOMAdA CASE PRESENTATION L. Martorano*1, P. Ogbogu2, K. Strothman3, 1. Columbus, OH; 2. Chagrin Falls, OH; 3. Plain City, OH. Background: The differential of hypereosinophilia is broad and includes atopy, infection, malignancy, and in rare cases of exclusion, hypereosinophilic syndrome (HES). Thorough evaluation is necessary to elucidate the cause and prevent sequelae of hypereosinophilia. Case Presentation: A 17-year-old male with a history of asthma, allergic rhinitis and depression presented with a 2-month history of fever, fatigue and night sweats. Labs were significant for leukocytosis with an AEC of 20,000. All new medications were discontinued. Infectious including parasitic work up was unremarkable. Chest CT revealed hilar and mediastinal lymphadenopathy. FNA biopsy of a pulmonary lymph node and bone marrow biopsy revealed no evidence of malignancy. Flow cytometry, cytogenetics, karyotyping, and mutation analysis for PDGFRA/B, FGFR1, and JAK 2 were unremarkable. The patient was given a presumptive diagnosis of idiopathic HES; however, did not respond to high dose steroid therapy or hydroxyurea. Further imaging was obtained and PET scan showed diffuse uptake in lung and abdominal lymph nodes with concern for marrow involvement. Excisional biopsy of an abdominal mesenteric lymph node revealed mixed inflammatory infiltrate with scattered atypical cells and binucleate Reed-Sternberg cells, confirming Nodular Sclerosis Hodgkin lymphoma. The patient was started on appropriate chemotherapy with dramatic improvement in his AEC. Discussion: HES is rare and is a diagnosis of exclusion. Lack of response to typical HES therapies should prompt investigation for underlying malignancy or other causes. Eosinophilia may be seen in nearly 15% of cases of Hodgkin’s lymphoma. Delay in diagnosis can lead to morbidity and mortality.
P276 HOMOZYGOUS TRNT1 (TRNA NUCLEOTIDYL TRANSFERASE 1) MUTATION IN A PATIENT WITH PYROPOIKILOCYTOSIS AND HUMORAL IMMUNODEFICIENCY R. Eisenberg1, R. Mehta1, A. Schneider*2, J. Shliozberg2, 1. Bronx, NY; 2. New York, NY. Introduction: Mutation of TRNT1 can lead to sideroblastic anemia, developmental delay, sensorineural hearing loss, periodic fevers, and hypogammaglobulienmia. We describe a unique presentation of homozygous TRNT1 mutation. Methods: Case Report Results: A 9 year old girl with hereditary pyropoikilocytosis and hypogammaglobuliemia initially presented with recurrent viral gastroenteritis, pneumonias and complex febrile seizures. Metabolic and vasculitic screening was negative. MRI showed subcortical infarcts and periventricular ischemia secondary to severe hemolytic anemia versus acute disseminated encephalomyelitis. Her seizures
resolved with steroids and keppra. Immune workup at age 3 revealed hypogammaglobulinemia with poor specific antibody responses for which patient started subcutaneous immunoglobulin (SCIG) and infections improved. SCIG was discontinued at age 9 with subsequent evaluation revealing normal immunoglobulin levels and 13/23 protective antibodies to streptococcus pneumonia post-vaccination. One year after SCIG she was admitted for dehydration secondary to viral gastroenteritis and developed epileptic encephalopathy, cardiac arrest, brain infarctions and subsequent bilateral sensorineural hearing loss. Infectious, vasculitic and autoimmune work-up was negative. She improved with IVIG and methylprednisolone, however hearing loss persisted. The following three months she was admitted for rhinovirus and two pneumonias treated with IVIG and antibiotics. Final admission was complicated by status epilepticus and severe hypoxemia leading to brain death. Autopsy showed cerebral edema with tonsillar herniation, encephalomalacia, hemorrhages, and non-perfused brain. Whole exome sequencing revealed a homozygous mutation in TRNT1. Conclusion: We describe a unique case of TRNT1 mutation presenting with pyropoikilocytosis and specific antibody deficiency who had a rapid decompensation with recurrent pneumonias and intractable seizures of unknown etiology eventually leading to her death.
P277 HYPEREOSINOPHILIA WITH SYSTEMIC SYMPTOMS DUE TO PINWORM V. Nanagas*, J. Montejo, Ann Arbor, MI. Introduction: Enterobiasis is the most common helminthic infection in the U.S. Most patients are asymptomatic but can classically present with perianal itching. Reports of eosinophilic gastrointestinal disease causing abdominal symptoms due to significant worm burden exist, but peripheral eosinophilia is rare. Other cases of enterobiasis describe eosinophilia; however, counts do not reach hypereosinophilic levels, with one exception (absolute eosinophil count (AEC) of 1.9 was found in an asymptomatic adult.) We present a pediatric patient with chronic systemic symptoms who developed hypereosinophilia (AEC 3.0) due to pinworm infection. Methods: An 8-year non-atopic girl presented for hypereosinophilia, intermittent fevers, headaches, weakness for 9 months. Extensive work-up for malignancy, inflammatory myopathies, kidney and gastrointestinal disease, cultures, were negative except for AEC 1.1, otherwise normal counts. Repeat AEC was 2.2 after one month and 3.0 one week later. Medical history includes migraines, recurrent UTIs. Results: Work-up for HES, end organ damage was normal including peripheral blood smear, strongyloides and toxocara titers, serum B12, troponin, echocardiography, CXR, flow cytometry, total IgE, tryptase, ANA, CRP, ESR, and stool studies for ova and parasites. She then presented to the ER with significant rectal pain, no pruritus. On perianal exam, a significant number of pinworms were present. Treatment with pyrantel pamoate resulted in resolution of symptoms and a subsequent AEC of 0.4. Conclusions: We report a case of hypereosinophilia (AEC to 3.0) with systemic symptoms due to pinworm infection in a pediatric patient. The differential for hypereosinophilia should include enterobius vermicularis. The scotch tape method may decrease need for further work-up.
P278 ALTERATION OF SERUM IMMUNOGLOBULIN CONCENTRATIONS IN DYSLIPIDEMIA M. Rusay, M. Bridgeman, M. Patel, L. Brunetti*, Piscataway, NJ. Introduction: Altered serum immunoglobulin (Ig) concentrations are implicated in cardiometabolic disease. Understanding the
P271 EXPERIENCE WITH TWO PATIENTS WITH ACTIVATED PI3K DELTA SYNDROME: CASE REPORTS A. Stoner*, J. Kennedy, A. Berlinski, S. Jones, A. Scurlock, Little Rock, AR. Introduction: Activated Phosphoinositide-3 Kinase (PI3k) delta syndrome (APDS) is a combined immunodeficiency caused by gain of function mutations in PIK3 protein or receptor. We present two patients with APDS, one protein (APDS1) and one receptor mutation (APDS2). Methods: Chart reviews detailed both patients’ clinical presentation and course, pulmonary function tests (PFTs), bronchoscopies, and immunologic/genetic testing. Results: Patient 1 is a male who presented at age 3 years with frequent infections and combined immunodeficiency. At 9yo, he developed bowel obstruction secondary to abdominal lymphoproliferation. PET scans of the lungs showed right sided consolidative mass and increased peri-tracheal lymphadenopathy. PFTs showed FVC 100%, FEV1 105%, and FEV1/FVC 96. Bronchoscopy revealed nodularity of main stem and segmental bronchi. Genetic testing showed a heterozygous missense mutation of APDS-1 (APDS1). He started sirolimus with improvement in clinical symptoms and reduced lymphoproliferation observed on bronchoscopy. Patient 2 is a female who presented at age 3 years with recurrent infections, increased IgM and antibody deficiency. At age 8 years, she developed upper airway lymphoproliferation, requiring numerous tonsillar debulking procedures. Bronchoscopy revealed nodularity and significant narrowing of left mainstem bronchus. PFTs showed FVC 66%, FEV1 68% and FEV1/FVC 93, a moderate restrictive pattern. Genetic testing showed a de novo autosomal dominant heterozygous variant in PIK3R1 gene (APDS2). She started sirolimus, and bronchoscopy improved, but PFTs remained unchanged. Conclusion: Both APDS patients presented with immune deficiency and lymphoproliferation; however, our patient with APDS2 resulting from mutation in PIK3R1 had a more severe clinical course requiring aggressive surgical management as well as immunomodulatory therapy.
vitro activation, confirming the diagnosis of XHIGM. His cutaneous warts remain recalcitrant. Conclusion: Susceptibility to viral infections is not a hallmark of XHIGM. This case of severe cutaneous warts represents an unusual presentation for CD40L deficiency.
P273 A CASE OF AGAMMAGLOBULINEMIA ATTRIBUTED TO HETEROZYGOUS, DOMINANT-NEGATIVE MUTATION IN TRANSCRIPTION FACTOR E47 E. Feuille*, B. Boisson, Y. Itan, J. Casanova, C. Cunningham-Rundles, New York, NY. Background: The majority of patients with early-onset infections and agammaglobulinemia have recessive mutations that impair downstream signaling through the B cell- and pre-B cell-receptors. One previous study identified 4 unrelated agammaglobulinemic patients with a dominant-negative mutation in the TCF3 gene encoding transcription factor E47, resulting in mutant protein E555K. Here we describe the case of a patient found to have this same mutation. Case Presentation: The patient initially presented at 4 years of age with chronic sinusitis and recurrent otitis. His immunoglobulins were undetectable; testing for BTK mutation was negative. After starting on monthly infusions of immunoglobulin, his symptoms improved. Other than occasional diarrhea and sinus infections 3 to 4 times per year, he has had an uncomplicated course until his current age of 26 years. His parents, brother, and three sisters are all without evidence of immunodeficiency. B cell count on most recent lymphocyte screen was 1/cu mm. On whole-exome sequencing, he was found to have heterozygous missense mutation in the TCF3 gene for E47, with resultant mutant protein E555K. Conclusions: This case report provides further evidence that E47 is critical in B cell development, and that a heterozygous mutation in E47 is associated with autosomal dominant agammaglobulinemia. With this patient sharing the same mutation with 4 previously described cases, this case supports the assertion that a mutational “hot-spot” exists in the E47 gene. Identification of this mutation may have prognostic value and will guide genetic counseling.
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P274
DISSEMINATED CUTANEOUS WARTS IN X-LINKED HYPER-IGM SYNDROME: A CASE REPORT H. Ho*, C. Cunningham-Rundles, New York, NY.
NOVEL DEDICATOR OF CYTOKINESIS 8 (DOCK8) MUTATION IN CHILD WITH ECZEMA AND RECURRENT SKIN ABSCESSES O. Waqar*1, B. Kaplan2, 1. Dix Hills, NY; 2. Great Neck, NY.
Introduction: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency caused by mutations in the CD40Ligand (CD40L) gene, leading to defective immunoglobulin class-switch recombination and impaired T-cell activation. Well-known manifestations of the syndrome include recurrent sinopulmonary infections, gastrointestinal complications, and neuroendocrine tumors. Cutaneous warts have rarely been reported in XHIGM. Case Presentation: We report a case of chronic disseminated warts in a 49-year-old male with hypogammaglobulinemia. The patient was diagnosed with primary antibody deficiency (IgG: 107mg/dL, IgA: 70mg/dL, and IgM: 70mg/dL) at age 3 in the setting of frequent sinopulmonary infections. There was no family history of immunodeficiency. He developed cutaneous warts at age 5, with increased severity since age 12. Physical exam was remarkable for warts covering his trunk and extremities, as well as coalesced warts forming thick hyperkeratotic plaques on his hands and feet. He failed multiple treatments including peg-interferon alpha and intralesional candida immunotherapy. His history was notable for HPV-negative urothelial carcinoma at age 42 and presumed diagnosis of common variable immunodeficiency since childhood. Due to his unusual presentation, whole exome sequencing was sent and it revealed a pSer214 frameshift mutation in his CD40L gene and carrier status in his mother. Flow cytometry analysis demonstrated a lack of CD40L expression on the surface of CD4+ T-cells upon in
S69
Introduction: DOCK8 deficiency is an autosomal recessive combined immunodeficiency syndrome associated with recurrent infections, eczema and other atopic diseases. The infections are usually viral, bacterial and fungal resulting in predominantly cutaneous and sinopulmonary manifestations. Homozygous or compound heterozygous deletions or mutations in the DOCK8 gene (9p24) lead to abnormal cytoskeletal organization and impaired function of dendritic cells and lymphocytes. Case Presentation: We present a three-year-old male with moderate-severe eczema, asthma, peanut and egg allergy who suffered from recurrent skin abscesses. Other infectious history included otitis media. There was no history of pneumonia or other severe infections. Skin abscesses responded to oral antibiotics, but recurred shortly after completing extended courses of treatment. The skin abscesses did not recur while the patient was on prophylactic antibiotics. Abscess cultures grew Enterococcus faecalis and Staphylococcus aureus. Laboratory results including quantitative immunoglobulins, specific antibody titers, myeloperoxidase staining, neutrophil oxidative burst and complement were within normal limits. IgE was elevated (6740 IU/mL) and there was a mild eosinophilia (1200 eosinophils/microL). T and B cell enumeration was essentially unremarkable with mild elevations in CD3 and CD4. DOCK8 genetic sequencing by GeneDx revealed a heterozygous
S70
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 119 (2017) S17eS96
missense mutation in exon 17 (c.1979 C>A, amino acid change p.Ala660Asp). Conclusion: The need for long term antibiotics to control recurrent skin abscesses should raise suspicion for an underlying immunodeficiency. DOCK8 deficiency should be considered in patients with severe eczema and recurrent abscesses despite appropriate antibiotics. The p.Ala660Asp missense mutation in the DOCK8 gene may represent a novel pathogenic variant.
P275 REFRACTORY HYPEREOSINOPHILIA MANIFESTING AS NODULAR SCLEROSIS CLASSICAL HODGKIN LYMPHOMAdA CASE PRESENTATION L. Martorano*1, P. Ogbogu2, K. Strothman3, 1. Columbus, OH; 2. Chagrin Falls, OH; 3. Plain City, OH. Background: The differential of hypereosinophilia is broad and includes atopy, infection, malignancy, and in rare cases of exclusion, hypereosinophilic syndrome (HES). Thorough evaluation is necessary to elucidate the cause and prevent sequelae of hypereosinophilia. Case Presentation: A 17-year-old male with a history of asthma, allergic rhinitis and depression presented with a 2-month history of fever, fatigue and night sweats. Labs were significant for leukocytosis with an AEC of 20,000. All new medications were discontinued. Infectious including parasitic work up was unremarkable. Chest CT revealed hilar and mediastinal lymphadenopathy. FNA biopsy of a pulmonary lymph node and bone marrow biopsy revealed no evidence of malignancy. Flow cytometry, cytogenetics, karyotyping, and mutation analysis for PDGFRA/B, FGFR1, and JAK 2 were unremarkable. The patient was given a presumptive diagnosis of idiopathic HES; however, did not respond to high dose steroid therapy or hydroxyurea. Further imaging was obtained and PET scan showed diffuse uptake in lung and abdominal lymph nodes with concern for marrow involvement. Excisional biopsy of an abdominal mesenteric lymph node revealed mixed inflammatory infiltrate with scattered atypical cells and binucleate Reed-Sternberg cells, confirming Nodular Sclerosis Hodgkin lymphoma. The patient was started on appropriate chemotherapy with dramatic improvement in his AEC. Discussion: HES is rare and is a diagnosis of exclusion. Lack of response to typical HES therapies should prompt investigation for underlying malignancy or other causes. Eosinophilia may be seen in nearly 15% of cases of Hodgkin’s lymphoma. Delay in diagnosis can lead to morbidity and mortality.
P276 HOMOZYGOUS TRNT1 (TRNA NUCLEOTIDYL TRANSFERASE 1) MUTATION IN A PATIENT WITH PYROPOIKILOCYTOSIS AND HUMORAL IMMUNODEFICIENCY R. Eisenberg1, R. Mehta1, A. Schneider*2, J. Shliozberg2, 1. Bronx, NY; 2. New York, NY. Introduction: Mutation of TRNT1 can lead to sideroblastic anemia, developmental delay, sensorineural hearing loss, periodic fevers, and hypogammaglobulienmia. We describe a unique presentation of homozygous TRNT1 mutation. Methods: Case Report Results: A 9 year old girl with hereditary pyropoikilocytosis and hypogammaglobuliemia initially presented with recurrent viral gastroenteritis, pneumonias and complex febrile seizures. Metabolic and vasculitic screening was negative. MRI showed subcortical infarcts and periventricular ischemia secondary to severe hemolytic anemia versus acute disseminated encephalomyelitis. Her seizures
resolved with steroids and keppra. Immune workup at age 3 revealed hypogammaglobulinemia with poor specific antibody responses for which patient started subcutaneous immunoglobulin (SCIG) and infections improved. SCIG was discontinued at age 9 with subsequent evaluation revealing normal immunoglobulin levels and 13/23 protective antibodies to streptococcus pneumonia post-vaccination. One year after SCIG she was admitted for dehydration secondary to viral gastroenteritis and developed epileptic encephalopathy, cardiac arrest, brain infarctions and subsequent bilateral sensorineural hearing loss. Infectious, vasculitic and autoimmune work-up was negative. She improved with IVIG and methylprednisolone, however hearing loss persisted. The following three months she was admitted for rhinovirus and two pneumonias treated with IVIG and antibiotics. Final admission was complicated by status epilepticus and severe hypoxemia leading to brain death. Autopsy showed cerebral edema with tonsillar herniation, encephalomalacia, hemorrhages, and non-perfused brain. Whole exome sequencing revealed a homozygous mutation in TRNT1. Conclusion: We describe a unique case of TRNT1 mutation presenting with pyropoikilocytosis and specific antibody deficiency who had a rapid decompensation with recurrent pneumonias and intractable seizures of unknown etiology eventually leading to her death.
P277 HYPEREOSINOPHILIA WITH SYSTEMIC SYMPTOMS DUE TO PINWORM V. Nanagas*, J. Montejo, Ann Arbor, MI. Introduction: Enterobiasis is the most common helminthic infection in the U.S. Most patients are asymptomatic but can classically present with perianal itching. Reports of eosinophilic gastrointestinal disease causing abdominal symptoms due to significant worm burden exist, but peripheral eosinophilia is rare. Other cases of enterobiasis describe eosinophilia; however, counts do not reach hypereosinophilic levels, with one exception (absolute eosinophil count (AEC) of 1.9 was found in an asymptomatic adult.) We present a pediatric patient with chronic systemic symptoms who developed hypereosinophilia (AEC 3.0) due to pinworm infection. Methods: An 8-year non-atopic girl presented for hypereosinophilia, intermittent fevers, headaches, weakness for 9 months. Extensive work-up for malignancy, inflammatory myopathies, kidney and gastrointestinal disease, cultures, were negative except for AEC 1.1, otherwise normal counts. Repeat AEC was 2.2 after one month and 3.0 one week later. Medical history includes migraines, recurrent UTIs. Results: Work-up for HES, end organ damage was normal including peripheral blood smear, strongyloides and toxocara titers, serum B12, troponin, echocardiography, CXR, flow cytometry, total IgE, tryptase, ANA, CRP, ESR, and stool studies for ova and parasites. She then presented to the ER with significant rectal pain, no pruritus. On perianal exam, a significant number of pinworms were present. Treatment with pyrantel pamoate resulted in resolution of symptoms and a subsequent AEC of 0.4. Conclusions: We report a case of hypereosinophilia (AEC to 3.0) with systemic symptoms due to pinworm infection in a pediatric patient. The differential for hypereosinophilia should include enterobius vermicularis. The scotch tape method may decrease need for further work-up.
P278 ALTERATION OF SERUM IMMUNOGLOBULIN CONCENTRATIONS IN DYSLIPIDEMIA M. Rusay, M. Bridgeman, M. Patel, L. Brunetti*, Piscataway, NJ. Introduction: Altered serum immunoglobulin (Ig) concentrations are implicated in cardiometabolic disease. Understanding the