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P187 Hematopoietic stem cell transplantation in a patient with griscelli syndrome type 2: case report
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Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
underlying mechanism of GOF STAT3 mutations and to evaluate for therapeutic options.
P187 HEMATOPOIETIC STEM CELL TRANSPLANTATION IN A PATIENT WITH GRISCELLI SYNDROME TYPE 2: CASE REPORT L. Lopez*, M. Mogica, Mexico City, DF, Mexico. Griscelli syndrome type 2 (GS-2) is a rare disorder belonging to the group of immune dysregulation. It is an autosomal recessive disease characterized by partial albinism with variable immunodeficiency. Grayish-silver hair with large and clumped melanosomes in hair shafts are diagnostic. The most frequent complication that leads to mortality includes lymphohistiocytic proliferation in several organs including the brain, but an early hematopoietic stem cell transplantation (HSCT) is the definitive treatment, therefore early recognition and treatment of GS-2 is critical. We present the case of a girl with GS-2 in which HSCT was successful. Clinical Case: Female child with a family history of parent consanguinity and a dead sibling because of complications after HSCT with diagnostic of Griscelli syndrome confirmed by mutation of gene RAB27A. Within the first year of life, she presented change in the color of her hair to a silveryish tone with an event of bronchitis associated with neutropenia. Confirmation of the homozygothic mutation of gene RAB27A and Griscelli syndrome diagnostic was done. She was proposed for HSCT, which was done in May 9th, 2013 (at the age of one year three months) from umbilical cord cells with compatibility 4/6, CD34+ 41.3x105, engraftment was achieved at day +13, without complications. Immunoglobulin 400mg/kg/do every four weeks during six months was given to prevent infectious diseases as IgG was in the borderline. At 4 years follow-up, she has been without infections, neurological deficit or accelerated hemophagocytic syndrome, showing that early recognition and treatment with HSCT is critical for an excellent prognosis.
P188 UNIQUE HETEROZYGOUS PRESENTATION IN AN INFANT WITH DNA LIGASE IV SYNDROME N. Dave*, B. Brunet, C. Carroll, O. Abdul-Rahman, M. Famuyide, Jackson, MS. Introduction: Ligase IV (LIG4) syndrome is a rare autosomal recessive disorder associated with impaired DNA damage response mechanisms resulting in a variety of clinical presentations. In 27 cases reported, various genetic mutations have been described. We present a case with a previously unidentified mutation. Methods: A newborn African American female with history of prematurity, IUGR, microcephaly, microsomia, and multiple dysmorphic features showed an inconclusive newborn TREC screen. She was further investigated for immunodeficiency. Results: Complete blood counts performed over 12 months demonstrated progressive development of leukopenia, marked lymphopenia, with normal thrombocytes and hemoglobin. Lymphocyte subsets were abnormal, producing a T-B-NK+ phenotype, with normal response to mitogens and specific antigens. Quantitative immunoglobulins showed low IgA and IGG subclasses. Specific antibody response to polysaccharide antigen was impaired, while maintaining good response to protein antigen. Genetic Sequence Slice identified two heterozygous changes in the gene LIG4 (c.1904delA, a known pathogenic frameshift mutation, and c.907G>C, a variant previously unidentified in LIG4 syndrome). Mother’s genetics show the presence of heterozygous c.1904delA gene. Father is not available for testing. She began trimethoprim/sulfamethoxazole prophylaxis at one month of age,
acyclovir was added upon diagnosis, and she has remained free of infection. IVIG therapy was started, and we plan for HSCT in the near future. Conclusion: While the second LIG4 variant is novel paired with a known pathogenic mutation, the phenotype fits and should be considered as disease causing until proven otherwise. Therefore, we describe a novel mutation in LIG4 associated with the classic phenotype of DNA Ligase IV syndrome.
P189 ATM PROTEIN, DOCK8, AND ZAP70 HETEROZYGOUS MUTATIONS PRESENTING AS ABNORMAL T-CELL RECEPTOR EXCISION CIRCLE VALUES Y. Lee*1, T. Gavrilova2, 1. Bronx, NY; 2. Newark, NJ. Introduction: Abnormal T-cell receptor excision circle (TREC) values on a newborn screen (NBS) can reflect severe combined immunodeficiency (SCID) or another form of T cell lymphopenia. We report a case of multiple heterozygous mutations in the absence of T cell lymphopenia that resulted in low TREC values on NBS. Presentation: A 14-day-old ex-40 weeker boy was referred to the Immunology clinic because of an abnormal TREC value on NBS. Results: The patient had abnormal TREC values (71, 0, 0, average 24). Lymphocyte subsets were significant for B cells within the low range of normal (CD19: 7%, absolute count 404 cells/uL). SCID panel revealed heterozygous mutations of two possible SCID-related genes, ZAP70 and duplication of DOCK8, and one gene related to ataxia-telangiectasia, ATM. These heterozygous mutations were of unknown clinical significance. At birth, the patient had eosinophilia (12%, absolute count 1800/uL) and elevated IgM (41.5mg/dL) but normal IgE levels (13.8 IU/mL) and negative hyper IgE and IgM genetic panels. At 6 months of age, he developed facial telangiectasias with mildly elevated alphafetoprotein (11.2 ng/mL). Considering his heterozygous ATM mutation he was referred for a neurological assessment, which was within normal limits, and a subsequent MRI of the brain was negative. ATM protein will be sent for qualitative analysis of presence and function. Conclusions: Multiple heterozygous mutations may result in abnormal TREC values. Low TREC values may not always be indicative of T cell lymphopenia. Heterozygous ATM mutations may result in an abnormal phenotype that should be monitored.
P190 DISSEMINATED MYCOBACTERIUM AVIUM INTRACELLULARE LEADING TO PROTEIN-LOSING GASTROENTEROPATHY IN AN ELDERLY WITH ISOLATED CD4 LYMPHOPENIA E. Arroyo-Flores*1, C. Perez1, M. Rodriguez-Roa2, W. Cosme-Blanco1, D. Ortiz1, S. Nazario1, 1. San Juan, Puerto Rico; 2. Dorado, PR. Rationale: Idiopathic CD4+ lymphocytopenia (ICL) is a rare cause of lymphopenia, characterized by opportunistic infections, lymphoproliferative malignancies or autoimmunity. We describe a rare case of an elderly man with late onset ICL who developed disseminated Mycobacterium avium intracellulare (MAI) and secondary protein-losing gastroenteropathy (PLG). Methods: Case Report Results: A 64-year-old male presented with 2 years history of recurrent fungal skin nodules positive to Aureobasidium spp., Alternaria spp., and Hortaea werneki. Persistent severe lymphopenia was noted and ICL suspected. He gradually developed 20 pounds weight loss and asymptomatic bilateral non-calcified pulmonary nodules. Bone marrow aspiration and PET scan were negative for malignancy. Upon follow up, 3 months later, he only complained of abdominal pain and
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
underlying mechanism of GOF STAT3 mutations and to evaluate for therapeutic options.
P187 HEMATOPOIETIC STEM CELL TRANSPLANTATION IN A PATIENT WITH GRISCELLI SYNDROME TYPE 2: CASE REPORT L. Lopez*, M. Mogica, Mexico City, DF, Mexico. Griscelli syndrome type 2 (GS-2) is a rare disorder belonging to the group of immune dysregulation. It is an autosomal recessive disease characterized by partial albinism with variable immunodeficiency. Grayish-silver hair with large and clumped melanosomes in hair shafts are diagnostic. The most frequent complication that leads to mortality includes lymphohistiocytic proliferation in several organs including the brain, but an early hematopoietic stem cell transplantation (HSCT) is the definitive treatment, therefore early recognition and treatment of GS-2 is critical. We present the case of a girl with GS-2 in which HSCT was successful. Clinical Case: Female child with a family history of parent consanguinity and a dead sibling because of complications after HSCT with diagnostic of Griscelli syndrome confirmed by mutation of gene RAB27A. Within the first year of life, she presented change in the color of her hair to a silveryish tone with an event of bronchitis associated with neutropenia. Confirmation of the homozygothic mutation of gene RAB27A and Griscelli syndrome diagnostic was done. She was proposed for HSCT, which was done in May 9th, 2013 (at the age of one year three months) from umbilical cord cells with compatibility 4/6, CD34+ 41.3x105, engraftment was achieved at day +13, without complications. Immunoglobulin 400mg/kg/do every four weeks during six months was given to prevent infectious diseases as IgG was in the borderline. At 4 years follow-up, she has been without infections, neurological deficit or accelerated hemophagocytic syndrome, showing that early recognition and treatment with HSCT is critical for an excellent prognosis.
P188 UNIQUE HETEROZYGOUS PRESENTATION IN AN INFANT WITH DNA LIGASE IV SYNDROME N. Dave*, B. Brunet, C. Carroll, O. Abdul-Rahman, M. Famuyide, Jackson, MS. Introduction: Ligase IV (LIG4) syndrome is a rare autosomal recessive disorder associated with impaired DNA damage response mechanisms resulting in a variety of clinical presentations. In 27 cases reported, various genetic mutations have been described. We present a case with a previously unidentified mutation. Methods: A newborn African American female with history of prematurity, IUGR, microcephaly, microsomia, and multiple dysmorphic features showed an inconclusive newborn TREC screen. She was further investigated for immunodeficiency. Results: Complete blood counts performed over 12 months demonstrated progressive development of leukopenia, marked lymphopenia, with normal thrombocytes and hemoglobin. Lymphocyte subsets were abnormal, producing a T-B-NK+ phenotype, with normal response to mitogens and specific antigens. Quantitative immunoglobulins showed low IgA and IGG subclasses. Specific antibody response to polysaccharide antigen was impaired, while maintaining good response to protein antigen. Genetic Sequence Slice identified two heterozygous changes in the gene LIG4 (c.1904delA, a known pathogenic frameshift mutation, and c.907G>C, a variant previously unidentified in LIG4 syndrome). Mother’s genetics show the presence of heterozygous c.1904delA gene. Father is not available for testing. She began trimethoprim/sulfamethoxazole prophylaxis at one month of age,
acyclovir was added upon diagnosis, and she has remained free of infection. IVIG therapy was started, and we plan for HSCT in the near future. Conclusion: While the second LIG4 variant is novel paired with a known pathogenic mutation, the phenotype fits and should be considered as disease causing until proven otherwise. Therefore, we describe a novel mutation in LIG4 associated with the classic phenotype of DNA Ligase IV syndrome.
P189 ATM PROTEIN, DOCK8, AND ZAP70 HETEROZYGOUS MUTATIONS PRESENTING AS ABNORMAL T-CELL RECEPTOR EXCISION CIRCLE VALUES Y. Lee*1, T. Gavrilova2, 1. Bronx, NY; 2. Newark, NJ. Introduction: Abnormal T-cell receptor excision circle (TREC) values on a newborn screen (NBS) can reflect severe combined immunodeficiency (SCID) or another form of T cell lymphopenia. We report a case of multiple heterozygous mutations in the absence of T cell lymphopenia that resulted in low TREC values on NBS. Presentation: A 14-day-old ex-40 weeker boy was referred to the Immunology clinic because of an abnormal TREC value on NBS. Results: The patient had abnormal TREC values (71, 0, 0, average 24). Lymphocyte subsets were significant for B cells within the low range of normal (CD19: 7%, absolute count 404 cells/uL). SCID panel revealed heterozygous mutations of two possible SCID-related genes, ZAP70 and duplication of DOCK8, and one gene related to ataxia-telangiectasia, ATM. These heterozygous mutations were of unknown clinical significance. At birth, the patient had eosinophilia (12%, absolute count 1800/uL) and elevated IgM (41.5mg/dL) but normal IgE levels (13.8 IU/mL) and negative hyper IgE and IgM genetic panels. At 6 months of age, he developed facial telangiectasias with mildly elevated alphafetoprotein (11.2 ng/mL). Considering his heterozygous ATM mutation he was referred for a neurological assessment, which was within normal limits, and a subsequent MRI of the brain was negative. ATM protein will be sent for qualitative analysis of presence and function. Conclusions: Multiple heterozygous mutations may result in abnormal TREC values. Low TREC values may not always be indicative of T cell lymphopenia. Heterozygous ATM mutations may result in an abnormal phenotype that should be monitored.
P190 DISSEMINATED MYCOBACTERIUM AVIUM INTRACELLULARE LEADING TO PROTEIN-LOSING GASTROENTEROPATHY IN AN ELDERLY WITH ISOLATED CD4 LYMPHOPENIA E. Arroyo-Flores*1, C. Perez1, M. Rodriguez-Roa2, W. Cosme-Blanco1, D. Ortiz1, S. Nazario1, 1. San Juan, Puerto Rico; 2. Dorado, PR. Rationale: Idiopathic CD4+ lymphocytopenia (ICL) is a rare cause of lymphopenia, characterized by opportunistic infections, lymphoproliferative malignancies or autoimmunity. We describe a rare case of an elderly man with late onset ICL who developed disseminated Mycobacterium avium intracellulare (MAI) and secondary protein-losing gastroenteropathy (PLG). Methods: Case Report Results: A 64-year-old male presented with 2 years history of recurrent fungal skin nodules positive to Aureobasidium spp., Alternaria spp., and Hortaea werneki. Persistent severe lymphopenia was noted and ICL suspected. He gradually developed 20 pounds weight loss and asymptomatic bilateral non-calcified pulmonary nodules. Bone marrow aspiration and PET scan were negative for malignancy. Upon follow up, 3 months later, he only complained of abdominal pain and