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El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.
Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.
Assuntos
Humanos , Masculino , Lactente , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Medula Óssea/efeitos adversos , CiclofosfamidaRESUMO
Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.
El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndrome de Wiskott-Aldrich , Masculino , Criança , Humanos , Lactente , Transplante de Medula Óssea/efeitos adversos , Síndrome de Wiskott-Aldrich/terapia , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida , Doença Enxerto-Hospedeiro/etiologiaRESUMO
BACKGROUND: Wiskott-Aldrich syndrome is an Inborn Error of Immunity characterized by thrombocytopenia, small platelets, severe eczema, recurrent infections, tendency to autoimmune diseases and neoplasms. The diagnosis of the syndrome can be difficult, especially when platelets are of normal size. CASE REPORT: A three-year-old male patient was referred to a specialized sector of university hospital for presenting acute otitis media that progressed to sepsis by Haemophilus influenzae. At one month of age, he had been diagnosed with autoimmune thrombocytopenia, and splenectomy was performed at two years of age. During follow-up, three hospitalizations were necessary: an infection by Streptococcus pneumoniae, which progressed to sepsis; one due to exacerbation of eczema, isolating S. epidermidis; another due to fever of undetermined origin. The tests showed normal number of platelets after splenectomy, platelets always with normal size. At age four, tests were performed: IgE 3128 Ku/L; IgA, IgG, and normal anti-polysaccharide antibodies; decreased IgM; decrease CD19, TCD4, naïve T and B; increased TCD8; normal NK. A diagnostic hypothesis of "probable" WAS was made. Genetic research has identified the c.295C>T mutation in the WAS gene. CONCLUSIONS: The case reported expressed a new mutation in the SWA gene, characterized by clinical manifestations of the mild phenotype of Wiskott-Aldrich syndrome, with thrombocytopenia, platelets of normal size, and X-linked inheritance. It is important to establish the early diagnosis and treatment to offer a better quality of life in these patients.
ANTECEDENTES: El síndrome de Wiskott-Aldrich es un error innato de la inmunidad, distinguido por trombocitopenia, plaquetas pequeñas, eccema severo, infecciones recurrentes, y susceptibilidad a enfermedades autoinmunes y neoplasias. El diagnóstico es difícil de establecer, especialmente cuando las plaquetas son de tamaño normal. REPORTE DE CASO: Paciente masculino de 3 años, enviado al Hospital Universitario da Santa Casa de São Paulo, Brasil, por otitis media aguda, con evolución a sepsis por Haemophilus influenzae. Al mes de edad fue diagnosticado con trombocitopenia autoinmune, y a los 2 años se llevó a cabo explenectomía. Durante el seguimiento requirió tres hospitalizaciones: una por infección por Streptococcus pneumoniae, que evolucionó a sepsis; otra por exacerbación de eccema, aislándose S. epidermidis, y la última por fiebre de origen indeterminado. Las pruebas de laboratorio informaron: concentración de plaquetas dentro de los valores de referencia después de la esplenectomía, y de tamaño normal. A los 4 años se efectuaron nuevas pruebas, que reportaron: IgE 3128 kU/L; IgA, IgG y anticuerpos anti-polisacáridos normales; disminución de IgM y de CD19, TCD4, T y B vírgenes; aumento de TCD8; NK normales. Se sospechó el diagnóstico de síndrome de Wiskott-Aldrich. Mediante estudios de genética se identificó la mutación c.295C>T en el gen WAS. CONCLUSIONES: El caso aquí expuesto expresó una nueva mutación en el gen SWA, caracterizado por manifestaciones clínicas de fenotipo leve del síndrome de Wiskott-Aldrich, con trombocitopenia, plaquetas de tamaño normal y herencia ligada al cromosoma X. Es importante establecer el diagnóstico y tratamiento oportunos para ofrecer una mejor calidad de vida en estos pacientes.
Assuntos
Eczema , Sepse , Trombocitopenia , Síndrome de Wiskott-Aldrich , Humanos , Masculino , Mutação , Qualidade de Vida , Trombocitopenia/genética , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína da Síndrome de Wiskott-Aldrich/genética , Pré-EscolarRESUMO
RESUMEN Introducción: El síndrome de Wiskott-Aldrich, es una inmunodeficiencia primaria, poco frecuente heredada de forma recesiva ligado al cromosoma X. Está asociado a fenotipos clínicos variables que se correlacionan con el tipo de mutación presente en la proteína del síndrome de Wiskott-Aldrich. Objetivo: Examinar el caso de un paciente con diagnóstico de Wiskott Aldrich y presencia de una mutación no descrita anteriormente. Presentación del caso: Paciente masculino cuya sintomatología se inició a los tres meses de edad, con infecciones respiratorias recurrentes, lesiones purpúricas hemorrágicas tipo equimosis, eccema y plaquetopenia. El diagnóstico se confirmó al año de inicio de los síntomas con la detección de una mutación no descrita anteriormente, ubicada en el codón 88 de la proteína del síndrome de Wiskott-Aldrich (p. Y88X; c.264C > G), asociada a una variante clásica. Conclusiones: La identificación temprana, diagnóstico y estratificación del fenotipo, es esencial para reducir los eventos desfavorables y complicaciones de la afección. El estudio genético es el medio de confirmación diagnóstica definitivo para el síndrome, lo que permite aplicar el protocolo terapéutico más adecuado para este tipo de inmunodeficiencia.
ABSTRACT Introduction: Wiskott Aldrich syndrome is a primary immunodeficiency, rarely inherited in a recessive way and linked to the X chromosome. It is associated with variable clinical phenotypes that correlate with the type of mutation present in the Wiskott Aldrich syndrome protein. Objective: Examine the case of a patient diagnosed with Wiskott Aldrich and presence of a mutation not described above. Case presentation: Male patient whose symptoms began at three months of age, with recurrent respiratory infections, purpuric hemorrhagic lesions such as ecchymosis, eczema and platelettopenia. The diagnosis was confirmed one year of after the symptoms onset with the detection of a mutation not previously described, located in codon 88 of the Wiskott Aldrich syndrome protein (p. Y88X; c.264C>G), associated with a classical variant. Conclusions: Early identification, diagnosis and stratification of the phenotype is essential to reduce unfavorable events and complications of the condition. The genetic study is the mean of definitive diagnostic confirmation for the syndrome, which allows to apply the most appropriate therapeutic protocol for this type of immunodeficiency.
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RESUMEN El Síndrome de Wiskott-Aldrich es una inmunodeficiencia hereditaria poco frecuente, acompañada de trombocitopenia. Así mismo, el absceso de tiroides se presenta raras veces, dados los niveles de iodo, irrigación linfática y lo encapsulado del órgano. El objetivo del presente trabajo es presentar el caso de un paciente con absceso de la glándula tiroides, que además era portador de Síndrome de Wiskott-Aldrich. De sexo masculino y 21 años de edad, fue atendido en el Hospital León Cuervo Rubio, de Pinar del Río. Una semana antes había sufrido un ántrax en la espalda, seguido del aumento de volumen del cuello y signos de compresión, aunque sin indicios de sepsis. Durante la intervención quirúrgica se encontró absceso de la glándula tiroides. El tratamiento oportuno del absceso de tiroides evita consecuencias fatales en enfermos inmunodeprimidos, como el paciente presentado.
ABSTRACT Wiskott-Aldrich Syndrome is a rare inherited immunodeficiency, accompanied by thrombocytopenia. In addition, thyroid abscess occurs rarely, given the levels of iodine, lymphatic irrigation and the encapsulation of the organ. The objective of this work is to present the case of a patient with an abscess of the thyroid gland, who was also a carrier of Wiskott-Aldrich syndrome. A 21 years old male was treated at the León Cuervo Rubio Hospital, in Pinar del Río. A week earlier, he had suffered a anthrax on his back, followed by swelling in his neck and signs of compression, but with no signs of sepsis. During the surgical intervention, an abscess of the thyroid gland was found. Timely treatment of thyroid abscess avoids fatal consequences in immunodeficient patients, such as the patient presented.
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BACKGROUND: The Wiskott-Aldrich syndrome is a combined immunodeficiency associated with a syndrome linked to the X chromosome, which is characterized by eczema, recurrent infections, and thrombocytopenia. Other manifestations include autoimmune disorders such as hemolytic anemia or thrombocytopenic purpura mediated by the immune system, increased susceptibility to malignant tumors, including lymphoma or leukemia. CLINICAL CASE: A 7-year-old male patient with a diagnosis of Wiskott-Aldrich syndrome who was treated with intravenous gamma globulin, antimicrobial prophylaxis with trimethoprim/sulfamethoxazole, and fluconazole, as well as with prednisone and cyclosporine due to hemolytic anemia and uveitis. Suddenly, he presented a deviation of the left labial commissure, so he was hospitalized. The studies showed a giant aneurysm of the aorta root, ascending aorta, descending aorta, and right coronary aorta, with insidious cardiac symptoms; therefore, he was referred to the vascular surgery department. CONCLUSION: Vasculitis in Wiskott-Aldrich syndrome is rare and it is usually asymptomatic in early stages, so an annual cardiovascular evaluation should be performed in order to avoid the complications of an aneurysm, which can be deleterious in this type of immunodeficiency where the possibility of death from bleeding is high.
Antecedentes: El síndrome de Wiskott-Aldrich es una inmunodeficiencia combinada asociada al síndrome ligado al cromosoma X, que se caracteriza por eccema, infecciones de repetición y trombocitopenia. Otras manifestaciones son los trastornos autoinmunes como anemia hemolítica o púrpura trombocitopénica mediada por el sistema inmunológico y susceptibilidad incrementada a tumores malignos, como linfoma o leucemia. Caso clínico: Niño de siete años, con diagnóstico de síndrome de Wiskott-Aldrich, en quien se estableció tratamiento con gammaglobulina intravenosa, profilaxis antimicrobiana con trimetoprima-sulfametoxazol y fluconazol, así como prednisona y ciclosporina debido a anemia hemolítica y uveítis. De forma súbita presentó desviación de la comisura labial izquierda, por lo que fue hospitalizado. Los estudios indicaron aneurisma gigante de la raíz de la aorta, aorta ascendente, descendente y coronaria derecha, con sintomatología cardiaca insidiosa, por lo que fue referido al servicio de cirugía vascular. Conclusiones: La vasculitis en el síndrome de Wiskott Aldrich es poco común y suele ser asintomática en las fases iniciales, por ello debe realizarse evaluación cardiovascular anual para evitar complicaciones propias de un aneurisma, que pueden ser deletéreas en este tipo de inmunodeficiencia, en las cuales existe mayor riesgo de muerte por sangrado.
Assuntos
Aneurisma da Aorta Torácica/etiologia , Síndrome de Wiskott-Aldrich/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Criança , Humanos , MasculinoRESUMO
Resumen: Introducción: El Síndrome de Guillain-Barré (SGB) es raramente diagnosticado en lactantes menores de 1 año. Su asociación con el Síndrome de Wiskott Aldrich (SWA), es aún menos frecuente, y ha sido previa mente reportada sólo en dos pacientes a nuestro conocimiento. La hidrocefalia, es una complicación conocida, pero infrecuente del SGB. Objetivo: presentar el caso clínico de un lactante en el que se asocian las patologías de SGB, SWA e hidrocefalia. Caso Clínico: varon de 9 meses, portador de SWA hospitalizado en unidad de cuidados intensivos por hipotonía aguda y compromiso del estado gene ral. Evolucionó con parálisis fláccida, falla ventilatoria y arreflexia generalizada. Una punción lumbar mostró disociación albuminocitológica, y el estudio electrofisiológico mostró signos de polineuropatía desmielinizante severa. Se trató con inmunoglobulina, evolucionando en forma satisfactoria. Por bradicardia intermitente, se realizó tomografla axial computada cerebral (TAC), que mostró signos de una hidrocefalia aguda, manejada mediante válvula derivativa ventrículo peritoneal con favorable respuesta. En el largo plazo, se sometió a trasplante de médula ósea y debió ser reintervenido por complicaciones valvulares, sin embargo, su desarrollo psicomotor es normal sin secuelas neurológi cas evidentes hasta los 3 años. Conclusión: Presentamos el tercer caso de SGB en un paciente porta dor de SWA, destacando ser el primero de ellos en un lactante menor de 1 año. Adicionalmente, este niño presentó una hidrocefalia aguda como complicación del SGB. Consideramos relevante tener presente estas comorbilidades, debido a que su pronto diagnóstico y manejo oportuno, permiten una mejor recuperación neurológica y evitan complicaciones potencialmente letales.
Abstract: Introduction: Guillain-Barre Syndrome (GBS) is rarely diagnosed in the first year of life. The association of GBS with Wiskott-Aldrich syndrome (WAS) is even less frequent and has been previously reported in only two children to our knowledge. Hydrocephalus is a known but rare complication of GBS. Objective: To describe the case of an infant in which GBS, WAS and hydrocephalus appear clinically associated. Clinical Case: A nine-months-old male infant with a history of WAS was admitted to our ICU with acute hypotonia and poor general condition. He developed flaccid paralysis, absent deep tendon reflexes, and respiratory failure. A lumbar puncture showed albuminocytologic dissociation. GBS was suspected and an electromyography was performed, showing a demyelinating polyneuropathy. He was successfully treated with intravenous immunoglobulins. During hospitalization, he presented intermittent bradycardia, so a brain CT scan was performed, showing acute hydrocephalus which was managed through an external ventricular drain achieving favorable response. In the long term, the patient underwent bone marrow transplant and had to be reoperated due to valve-related complications. However, his psychomotor development is normal, with no obvious neurological sequelae. Conclusion: We present the third case of GBS in a patient with WAS, which is the first infant younger than one year. Additionally, he presented acute hydrocephalus as a complication of GBS. We suggest considering these three comorbidities since their early diagnosis and prompt management allow bet ter neurological recovery and avoid potentially lethal complications.
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Humanos , Masculino , Lactente , Síndrome de Wiskott-Aldrich/complicações , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Hidrocefalia/diagnóstico , Hidrocefalia/etiologiaRESUMO
The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.
Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência/terapia , Doenças Raras/terapia , Brasil/epidemiologia , Diagnóstico Tardio , Países em Desenvolvimento , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/mortalidade , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Doenças Raras/epidemiologia , Doenças Raras/mortalidade , Análise de SobrevidaRESUMO
A Síndrome de Wiskott-Aldrich (WAS) é uma imunodeficiência congênita ligada ao cromossomo X, caracterizada por mutações no gene WAS, responsável pela proteína WASP. As principais manifestações clínicas são trombocitopenia com plaquetas de volume reduzido, eczema, infecções recorrentes e maior incidência de doenças autoimunes e neoplasias. Relatamos o caso de um paciente do sexo masculino com sintomas clássicos desta síndrome (eczema, trombocitopenia e infecções recorrentes), porém com plaquetas de volume normal. Existem poucos relatos desta síndrome em pacientes com plaquetas de volume normal, o que atrasou o encaminhamento do paciente ao imunologista, o qual foi tratado como portador de Síndrome de Evans e dermatite atópica até os quatro anos de idade. A confirmação diagnóstica foi por teste genético. O diagnóstico precoce possibilita profilaxia com antibioticoterapia e uso de imunoglobulina endovenosa, devido ao risco de infecções graves, e encaminhamento para transplante de células-tronco hematopoiéticas, que até o momento é o único tratamento curativo. A suspeita clínica deve existir em pacientes com trombocitopenia inexplicável, mesmo se as plaquetas tiverem o tamanho normal, associada às outras manifestações da doença.
Wiskott-Aldrich syndrome (WAS) is an X-linked congenital immunodeficiency characterized by mutations in the WAS gene of the WASP protein. The main clinical manifestations are thrombocytopenia with small-sized platelets, eczema, recurrent infections and a higher incidence of autoimmune diseases and cancer. We report the case of a male patient with classical symptoms of this syndrome (eczema, thrombocytopenia and recurrent infections), however presenting platelets with normal size. There are few reports of this syndrome in patients with normal-sized platelets, which delayed our patient's referral to the immunologist. The patient received treatment for Evans syndrome and atopic dermatitis until he was four years old. Confirmation of WAS diagnosis was made by genetic testing. Early diagnosis allows prophylactic treatment with antibiotics and the use of intravenous immunoglobulin due to the risk of serious infections, in addition to referral for hematopoietic stem cell transplantation, which is the only curative treatment available so far. WAS should be suspected when patients develop unexplained thrombocytopenia even with normal-sized platelets, especially in the presence of other manifestations.
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Humanos , Pré-Escolar , Trombocitopenia , Síndrome de Wiskott-Aldrich , Plaquetas , Testes Genéticos , Transplante de Células-Tronco Hematopoéticas , Eczema , Sinais e Sintomas , Terapêutica , Imunoglobulinas Intravenosas , Proteína da Síndrome de Wiskott-Aldrich , Reinfecção , Infecções , MutaçãoRESUMO
BACKGROUND: Thrombocytopenia can occur in different circumstances during childhood and although immune thrombocytopenia is its most frequent cause, it is important to consider other conditions, especially when there is a persistent or recurrent low platelet count. We report two cases of intermittent thrombocytopenia, previously misdiagnosed as immune thrombocytopenia. CASES PRESENTATION: Both cases described were boys who presented with an intermittent pattern of thrombocytopenia, with a persistently low mean platelet volume. In both patients, peripheral blood smear revealed small platelets and flow cytometry showed low expression of Wiskott-Aldrich syndrome protein (WASP) in leucocytes. Molecular analysis of the first case identified a mutation in exon 2 of the gene coding for WASP, leading to a p.Thr45Met amino acid change and confirming the diagnosis of X-linked thrombocytopenia. In the second case, a novel missense mutation in exon 2 of the gene coding for WASP was detected, which resulted in a p.Pro58Leu amino acid change. CONCLUSION: These two rare presentations of thrombocytopenia highlight the importance of evaluating the peripheral blood smear in the presence of recurrent or persistent thrombocytopenia and show that failing to do so can lead to misdiagnoses. Since thrombocytopenia may be found in pediatric outpatient clinic, increased awareness among general pediatricians will help to improve the differential diagnosis of this condition.
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Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Trombocitopenia/diagnóstico , Proteína da Síndrome de Wiskott-Aldrich/genética , Pré-Escolar , Erros de Diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/sangue , Doenças Genéticas Ligadas ao Cromossomo X/genética , Marcadores Genéticos , Humanos , Lactente , Masculino , Mutação , Contagem de Plaquetas , Trombocitopenia/sangue , Trombocitopenia/genéticaRESUMO
El síndrome de Wiskott-Aldrich es una inmunodeficiencia primaria; con una incidencia de 3,5 a 5,2 por cada millón de recién nacidos masculinos. Se caracteriza por tener un patrón de herencia recesiva ligada al cromosoma X. En estos pacientes; se ha descrito la tríada clásica de inmunodeficiencia; microtrombocitopenia y eczema. Presentamos un paciente de 5 años de edad; hispánico; con antecedentes de numerosas infecciones desde el primer año de vida. Actualmente; presenta desnutrición crónica; talla baja secundaria y retraso en el desarrollo del lenguaje. Se diagnosticó una mutación poco frecuente del gen asociado al síndrome de Wiskott-Aldrich.
The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency, with an estimated incidence of 3.5 to 5.2 cases per million males. It is characterizedby immunodeficiency, microthrombocytopenia and eczema. We present a 5-year-old Hispanic male, with a medical history of numerous infectious diseases, compromised health, chronic malnutrition, language delay and failure to thrive. An infrequent mutation in the Wiskott-Aldrich syndrome gene was found.
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Animais , Embrião de Galinha , Proteínas Aviárias/metabolismo , Caderinas/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Proteínas Aviárias/antagonistas & inibidores , Proteínas Aviárias/genética , Sequência de Bases , Contagem de Células , Caderinas/antagonistas & inibidores , Caderinas/genética , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Tubo Neural/citologia , Tubo Neural/embriologia , Tubo Neural/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de SinaisRESUMO
El síndrome de Wiskott-Aldrich es una inmunodeficiencia primaria; con una incidencia de 3,5 a 5,2 por cada millón de recién nacidos masculinos. Se caracteriza por tener un patrón de herencia recesiva ligada al cromosoma X. En estos pacientes; se ha descrito la tríada clásica de inmunodeficiencia; microtrombocitopenia y eczema. Presentamos un paciente de 5 años de edad; hispánico; con antecedentes de numerosas infecciones desde el primer año de vida. Actualmente; presenta desnutrición crónica; talla baja secundaria y retraso en el desarrollo del lenguaje. Se diagnosticó una mutación poco frecuente del gen asociado al síndrome de Wiskott-Aldrich.(AU)
The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency, with an estimated incidence of 3.5 to 5.2 cases per million males. It is characterizedby immunodeficiency, microthrombocytopenia and eczema. We present a 5-year-old Hispanic male, with a medical history of numerous infectious diseases, compromised health, chronic malnutrition, language delay and failure to thrive. An infrequent mutation in the Wiskott-Aldrich syndrome gene was found.(AU)
Assuntos
Animais , Embrião de Galinha , Proteínas Aviárias/metabolismo , Caderinas/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Proteínas Aviárias/antagonistas & inibidores , Proteínas Aviárias/genética , Sequência de Bases , Caderinas/antagonistas & inibidores , Caderinas/genética , Contagem de Células , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Tubo Neural/citologia , Tubo Neural/embriologia , Tubo Neural/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de SinaisRESUMO
Over the last decades, research dedicated to the molecular and cellular mechanisms underlying primary immunodeficiencies (PID) has helped to understand the etiology of many of these diseases and to develop novel therapeutic approaches. Beyond these aspects, PID are also studied because they offer invaluable natural genetic tools to dissect the human immune system. In this review, we highlight the research that has focused over the last 20 years on T lymphocytes from Wiskott-Aldrich syndrome (WAS) patients. WAS T lymphocytes are defective for the WAS protein (WASP), a regulator of actin cytoskeleton remodeling. Therefore, study of WAS T lymphocytes has helped to grasp that many steps of T lymphocyte activation and function depend on the crosstalk between membrane receptors and the actin cytoskeleton. These steps include motility, immunological synapse assembly, and signaling, as well as the implementation of helper, regulatory, or cytotoxic effector functions. The recent concept that WASP also works as a regulator of transcription within the nucleus is an illustration of the complexity of signal integration in T lymphocytes. Finally, this review will discuss how further study of WAS may contribute to solve novel challenges of T lymphocyte biology.
RESUMO
Wiskott-Aldrich syndrome was first reported clinically in 1937, and in 1954 the classic triad was identified: eccema, recurrent infections and thrombocytopenia with an X-linked transmission. Its incidence is estimated at 1 to 10 in one million live births per year. Wiskott Aldrich syndrome is caused by mutations in a gene in the short arm of chromosome X that encodes the Wiskott-Aldrich syndrome protein (WASp), which identification and sequencing was first performed in 1994, and since then about 300 mutations have been reported. This paper describes the case of a boy with Wiskott-Aldrich syndrome, with clinical and genetic diagnosis, with a considerable diagnostic delay attributable to an atypical presentation misdiagnosed as immune thrombocytopenia.
El síndrome de Wiskott Aldrich fue descrito en 1937 y en 1954 se identificó su tríada característica: eccema, infecciones recurrentes y trombocitopenia, con herencia ligada al cromosoma X. Su incidencia se calcula en 1 a 10 por cada millón de recién nacidos vivos por año. Su causa es la mutación del gen localizado en el brazo corto del cromosoma X, que codifica la proteína del síndrome Wiskott-Aldrich (WASp), cuya identificación y secuenciación se realizan desde 1994, lo que ha permitido describir al menos 300 defectos genéticos. Comunicamos un caso de síndrome de Wiskott-Aldrich con diagnóstico clínico y genético, tipo nonsense Q203X, en el exón 7, en un preescolar con ausencia de eccema.
RESUMO
El síndrome de Wiskott Aldrich es una inmunodeficiencia primaria clasificada dentro del grupo de las bien definidas, se hereda con carácter recesivo ligado al X, el gen mutado codifica para una proteína citoplasmática presente en linfocitos y megacariocitos importante en la regulación de la polimerización de la actina y traducción de señales necesarias para la reorganización del citoesqueleto celular. Las manifestaciones clásicas están dadas por sangramientos, infecciones y eczemas; sus primeros síntomas pueden aparecer al nacimiento con hemorragia petequial, diarreas con sangre; mientras las infecciones y el eczema se desarrollan durante el primer año de edad, la otitis media es la infección que se presenta con mayor frecuencia. Desde el punto de vista inmunológico se caracteriza por tener niveles de inmunoglobulina M bajos, las inmunoglobulinas A y E son elevadas, mientras la inmunoglobulina G puede ser normal a lo que se une trombocitopenia. El diagnóstico de esta enfermedad se realizó en un niño de tres meses de edad, el cual permaneció ingresado por largo tiempo en cuidados intensivos y falleció a los dos años de edad por sepsis generalizada.
The Wiscott Aldrich Syndrome is a well-defined primary immunodeficiency X- linked recessive disorder, the mutated gene encodes a cytoplasmatic protein in lymphocytes and megakaryocytes which is important in actin polymerization and cytoskeletal reorganization .The classic manifestations involve bleeding, infections and eczema. The first symptoms may appear at birth with petechial hemorrhage, diarrhea with blood, while infections and eczema are present during the first year of age, otitis media is an infection that occurs more frequently. From the immunological point of view it is characterized by low levels immunoglobulin M, immunoglobulin A and E are high, while immunoglobulin G may be normal together with thrombocytopenia. This disorder was diagnosed in a three- year- month infant who was admitted at intensive care unit for a long period of time. The patient died when he was two years old due to generalized infection.