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BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) [OMIM 615513] is an inborn error of immunity with autosomal dominant inheritance caused by a pathogenic variant in the PIK3CD gene. The prevalence ratio of APDS is < 1: 1,000,000 newborns. The main clinical features of APDS are sinopulmonary infections, benign lymphoproliferation, autoinflammatory disease, and a major risk of lymphoid neoplasms. CLINICAL CASE: A 17-year-old female with a history of pneumonia at 9 months of age subsequently developed recurrent respiratory tract infections, bronchiectasis, perforated otitis media, unilateral tonsillar lymphoid hyperplasia, pansinusitis, recurrent oral candidiasis, and chronic rhinitis. Laboratory studies reported persistent leukopenia and lymphopenia, low CD4 lymphocyte subpopulation, and persistently elevated immunoglobulin M immunoglobulin studies with values up to 692 mg/dL. An inborn error of immunity next-generation sequencing and multiplex ligation-dependent probe amplification analysis detected a heterozygous pathogenic variant in the PIK3CD gene, compatible with APDS. Treatment with monthly injectable gamma globulin and prophylactic antibiotics was started, allowing better control of the infectious processes. CONCLUSION: This is the second case of APDS reported in Mexico in the literature. It is important to be aware of this condition to make a timely diagnosis, which requires a high clinical suspicion and immunological and genetic studies to provide adequate treatment and prevent complications.

INTRODUCCIÓN: El síndrome de la Fosfoinositida 3-cinasa delta activado (Activated Phosphoinositide 3-kinase δ síndrome, APDS) [OMIM 615513] es un error innato de la inmunidad con patrón de herencia autosómica dominante causada por una variante patogénica heterocigota del gen PIK3CD. Su prevalencia es < 1: 1,000,000 nacidos vivos. Las principales manifestaciones clínicas son infecciones sinopulmonares, linfoproliferación benigna, autoinmunidad y aumento del riesgo de malignización linfoide. CASO CLÍNICO: Femenino de 17 años de vida con antecedentes de neumonía a los 9 meses de edad, posteriormente infecciones de vías respiratorias recurrentes, bronquiectasias, otitis media perforada, hiperplasia linfoide de amigdala unilateral, pansinusitis, candidiasis oral recurrente y rinitis crónica. Los estudios de laboratorio reportaron leuco linfopenia persistente, subpoblación linfocitaria con CD4 baja y estudios de inmunoglobulinas con IgM persistentemente elevada con valor de hasta 692 mg/dl. Se realizó estudio molecular de secuenciación de siguiente generación (NGS por sus siglas en inglés Next-Generation Sequencing) y amplificación de sondas dependientes de ligandos múltiples (MLPA por sus siglas en inglés Multiplex Ligation-dependent Probe Amplification) dirigido a errores innatos de la inmunidad que detectó una variante patogénica en estado heterocigoto en el gen PIK3CD, compatible con APDS. Se inició tratamiento con gammaglobulina intravenosa mensual y antibiótico profiláctico, permitiendo mejor control de los procesos infecciosos. CONCLUSIONES: Este es el segundo caso reportado en la literatura de APDS en México, por lo que es importante su conocimiento para poder realizar un diagnóstico oportuno, para el cual se requiere una alta sospecha clínica, además de estudios inmunológicos y genéticos, con la finalidad de otorgar el tratamiento adecuado y prevenir complicaciones.

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Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin.

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Las inmunodeficiencias primarias constituyen un grupo de más de 300 enfermedades frecuentemente graves y a menudo mortales que reflejan un déficit cuantitativo o cualitativo en uno o más componentes del sistema inmunitario. Son el resultado de defectos genéticos heredados que suelen afectar a 1 de cada 8000 a 10 000 nacidos vivos. Las manifestaciones clínicas suelen ser muy variadas, debido a que en su mayoría presentan una amplia heterogeneidad genética: infecciones (comunes recurrentes, comunes graves, o raras y graves), inflamación, autoinmunidad, malignidad o alergia. Teniendo en cuenta que a los profesionales médicos de diversas especialidades les resulta difícil identificar cuándo están en presencia de una IDP, nos proponemos describir las características clínicas, epidemiológicas, inmunitarias y genéticas de las inmunodeficiencias primarias. Para la realización de la revisión bibliográfica se utilizaron 27 referencias bibliográficas(AU)

Primary immunodeficiencies constitute a group of more than 300 frequently serious and often fatal diseases that reflect a quantitative and / or qualitative deficit in one or more components of the immune system. They are the result of inherited genetic defects that usually affect 1 in 8,000 to 10,000 live births. The clinical manifestations are usually very varied, because they mostly have a wide genetic heterogeneity, they can be caused by infections (common recurring, common serious, or rare and serious), inflammation, autoimmunity, malignancy, or allergy. Given that medical professionals of various specialties find it difficult to identify when they are in the presence of an primary immunodeficiency, it is proposed as an objective: to describe the clinical, epidemiological, immunological and genetic characteristics of Primary immunodeficiency. For the literature review, 27 bibliographic references were used(AU)

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El Complejo de Esclerosis Tuberosa (CET) es un trastorno genético de heren-cia autosómica dominante causado por la mutación en uno de los genes TSC1 o TSC2. Los pacientes con una afectación CET grave de tipo neurológica posible-mente presentarán epilepsia, discapacidad intelectual, problemas específicos del aprendizaje y trastornos de la conducta, por lo que la evaluación neuropsicológica en individuos con esta patología cobra un carácter importante al proporcionar información sobre los déficits cognitivos que subyacen en la afectación cerebral, que alteran el funcionamiento intelectual y los aspectos adaptativos. El actual tra-bajo presenta el perfil de una paciente adulta femenina con antecedente de CET, epilepsia y discapacidad intelectual, así como la descripción de una propuesta de intervención neuropsicológica basada en el funcionamiento ejecutivo dorsolateral.

Tuberous Sclerosis Complex (TSC) is an autosomal dominant inherited genetic disorder caused by mutation in one of the TSC1 or TSC2 genes. Patients with severe neurological-type CET involvement may have epilepsy, intellectual disability, specific learning problems, and behavioral disorders. For this reason, the neuropsychological evaluation in individuals with this pathology becomes an important character by providing information on the cognitive deficits that underlie brain involvement that alter intellectual functioning and adaptive aspects. The current work presents the cognitive profile of a female adult patient with a history of TSC, epilepsy and intellectual disability and the description of a proposed neuropsychological intervention based on dorsolateral executive functioning.

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As imunodeficiências primárias (PIDs) são doenças genéticas que têm como principal característica alterações do sistema imune, caracterizadas por deficiências de desenvolvimento e/ou função desse sistema, levando o paciente à maior suscetibilidade às infecções de repetição, doenças auto-imunes e/ou neoplasias. Estão agrupadas como um único grupo de doenças e a sua classificação, varia de acordo com a natureza da deficiência imunológica subjacente, podendo ser por deficiências de anticorpos, imunodeficiências combinadas, desordens de células fagocitárias, entre outras. Estimam-se sua incidência entre 1:2.000 crianças nascidas vivas e o diagnóstico precoce dessas doenças, é essencial para a redução da morbidade e mortalidade desses pacientes. A identificação precoce e o tratamento eficiente das PIDs são pontos chaves para a sobrevivência e melhor qualidade de vida dos pacientes imunodeficientes, modificando de maneira decisiva o prognóstico destas doenças. Na busca de um diagnóstico mais rápido e eficaz, esse trabalho dispôs de uma análise multigênica de pacientes com pelo menos 1 dos 10 sinais de alerta para PID. Foram sequenciados e analisados 34 casos, sendo 25 do sexo masculino e 9 do sexo feminino. Utilizou-se ferramentas de nova geração e filtros específicos, baseados nos resultados do sequenciamento total do exoma, possibilitando assim , o diagnóstico de 7 casos de Agamaglobulinemia (gene BTK), 2 casos de Wiskott-Aldrich (gene WAS), 1 caso de Doença Granulomatosa Crônica (gene CYBB), 1 caso de Síndrome de Hiper-IgM do tipo I (gene CD40LG) e a investigação parental dos 23 casos sem diagnóstico concluído. Esses achados foram confirmados através do Sequenciamento de Sanger, considerado como padrão ouro para o estudo.

Primary immunodeficiencies are genetic diseases that have as main characteristic alterations of the immune system, characterized by deficiencies of development and / or function of this system, leading the patient to greater susceptibility to recurrent infections, autoimmune diseases and / or neoplasias. They are grouped as a single group of diseases and their classification varies according to the nature of the underlying immunological deficiency, and may be due to antibody deficiencies, combined immunodeficiencies, phagocytic cell disorders, among others. Their incidence is estimated between 1: 2000 live births and the early diagnosis of these diseases is essential to reduce the morbidity and mortality of these patients. Early identification and efficient treatment of PIDs are key points for the survival and better quality of life of immunodeficient patients, modifying the prognosis of these diseases in a decisive way. In the search for a faster and more effective diagnosis, this work had a multigenic analysis of patients with at least 1 of the 10 warning signs for PID. Thirty-four cases were sequenced and analyzed, of which 25 were male and 9 were female. New generation tools and specific filters were used based on the results of the complete exome sequencing, allowing the diagnosis of 7 cases of agammaglobulinemia (BTK gene), 2 cases of Wiskott-Aldrich (WAS gene), 1 case of disease Chronic Granulomatose (CYBB gene), 1 case of Type I Hyper-IgM Syndrome (CD40LG gene) and parental investigation of the 23 cases without a completed diagnosis. These findings were confirmed using the Sanger Sequencing, considered the gold standard for the study.

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