RESUMEN
El síndrome por deleción 22q11 (SD22q11) es el síndrome por deleción cromosómica más frecuente en humanos y se caracteriza por la tríada clínica que incluye cardiopatía congénita, hipocalcemia e inmunodeficiencia primaria. El 85-90% de los pacientes tienen microdeleciones en el cromosoma 22q11.2. Tomando como punto cardinal la cardiopatía congénita, se diseñó una estrategia para tamización y diagnóstico de SD22q11 con énfasis en la evaluación inmune. Es imprescindible realizar una historia clínica detallada y, posteriormente, un análisis cuantitativo y funcional de las subpoblaciones de linfocitos en sangre periférica para clasificarlo en SD22q11 completo (<1%) o parcial (95-99%) e instaurar las pautas de tratamiento en aspectos como: aislamiento del paciente, vacunación, profilaxis contra microorganismos oportunistas, uso de productos sanguíneos irradiados y reconstitución inmunológica. Sin embargo, el abordaje del paciente debe ser multidisciplinario para detectar y prevenir complicaciones a largo plazo que pueden ser graves, especialmente en los pacientes con SD22q11 completo.
22q11 deletion syndrome (SD22q11) is the most common chromosomal deletion syndrome in humans and is characterised by the clinical triad of congenital heart disease, hypocalcaemia and primary immunodeficiency. 85-90% of patients have microdeletions on chromosome 22q11.2. Taking congenital heart disease as a cardinal point, a strategy for screening and diagnosis of SD22q11 was designed with emphasis on immune assessment. A detailed clinical history and subsequent quantitative and functional analysis of peripheral blood lymphocyte subpopulations is essential to classify the patient as having complete (<1%) or partial (95-99%) SD22q11 and to establish treatment guidelines such as patient isolation, vaccination, prophylaxis against opportunistic microorganisms, use of irradiated blood products and immune reconstitution. However, the patient's approach must be multidisciplinary to detect and prevent long-term complications that can be severe, especially in patients with complete SD22q11.
Asunto(s)
Humanos , Síndrome de DiGeorge , Síndrome de Deleción 22q11 , Enfermedades del Sistema Endocrino , Cardiopatías Congénitas , Síndromes de Inmunodeficiencia , Linfopenia/congénitoRESUMEN
Glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency was recently defined as a new severe congenital neutropenia subgroup remarkable with congenital heart defects, urogenital malformations, endocrine abnormalities, and prominent superficial veins. Here, we report 3 patients with G6PC3 deficiency presenting with recurrent diarrhea, failure to thrive, and sinopulmonary infections leading to bronchiectasis. In patient I and II, a combined immune deficiency was suspected due to early-onset disease with lymphopenia, neutropenia, and thrombocytopenia, along with variable reductions in lymphocyte subpopulations and favorable response to intravenous γ-globulin therapy. Apart from neutropenia, all 3 patients had intermittent thrombocytopenia, anemia, and lymphopenia. All patients had failure to thrive and some of the classic syndromic features of G6PC3 deficiency, including cardiac abnormalities and visibility of superficial veins in all, endocrinologic problems in PI and PIII, and urogenital abnormalities in PII. Our experience suggests that a diagnosis of congenital neutropenia due to G6PC3 may not be as straightforward in such patients with combined lymphopenia and thrombocytopenia. A high index of suspicion and the other syndromic features of G6PC3 were clues to diagnosis. Screening of all combined immune deficiencies with neutropenia may help to uncover the whole spectra of G6PC3 deficiency.
Asunto(s)
Anomalías Múltiples/genética , Glucosa-6-Fosfatasa/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Síndromes de Inmunodeficiencia/genética , Subgrupos Linfocitarios/patología , Neutropenia/genética , Anomalías Múltiples/enzimología , Adolescente , Bronquiectasia/etiología , Dominio Catalítico , Linaje de la Célula , Niño , Codón sin Sentido , Colitis/enzimología , Colitis/genética , Consanguinidad , Diarrea/enzimología , Diarrea/genética , Exones/genética , Insuficiencia de Crecimiento/enzimología , Insuficiencia de Crecimiento/genética , Femenino , Mutación del Sistema de Lectura , Enfermedad del Almacenamiento de Glucógeno Tipo I/inmunología , Humanos , Síndromes de Inmunodeficiencia/enzimología , Linfopenia/congénito , Linfopenia/enzimología , Linfopenia/genética , Masculino , Mutagénesis Insercional , Neutropenia/enzimología , Linaje , Fenotipo , Sitios de Empalme de ARN/genética , Infecciones del Sistema Respiratorio/complicaciones , Trombocitopenia/congénito , Trombocitopenia/enzimología , Trombocitopenia/genética , TurquíaRESUMEN
Five days after birth of a viable Fell pony filly, yellow watery diarrhoea appeared without any signs of systemic disease. Four days later the diarrhoea ceased. On 11th day, the animal showed apathy, and a few days later, the foal was very lethargic, suffered from muscular weakness and severe watery diarrhoea that reappeared. The illness did not respond to therapy. At the age of 21 days the filly spontaneously died under symptoms of intestinal colic and pneumonia. Haematological examinations revealed lower numbers of erythrocytes as well as non-selective lymphopenia. Phagocytic activity was slightly increased, lymphocyte activity was inhibited. Histopathology showed severe alteration of the lymphatic organs. T and B lymphocytes and antigen-presenting macrophages were not arranged in characteristic areas, and the quantity of these cells was lower than would be expected. Histopathological changes in lymphatic organs resembled those described in the literature as severe combined immunodeficiency.