Uncovering the Relationship Between Genes and Phenotypes Beyond the Gut in Microvillus Inclusion Disease.

Microvillus inclusion disease (MVID) is a rare condition that is present from birth and affects the digestive system. People with MVID experience severe diarrhea that is difficult to control, cannot absorb dietary nutrients, and struggle to grow and thrive. In addition, diverse clinical manifestations, some of which are life-threatening, have been reported in cases of MVID. MVID can be caused by variants in the MYO5B, STX3, STXBP2, or UNC45A gene. These genes produce proteins that have been functionally linked to each other in intestinal epithelial cells. MVID associated with STXBP2 variants presents in a subset of patients diagnosed with familial hemophagocytic lymphohistiocytosis type 5. MVID associated with UNC45A variants presents in most patients diagnosed with osteo-oto-hepato-enteric syndrome. Furthermore, variants in MYO5B or STX3 can also cause other diseases that are characterized by phenotypes that can co-occur in subsets of patients diagnosed with MVID. Recent studies involving clinical data and experiments with cells and animals revealed connections between specific phenotypes occurring outside of the digestive system and the type of gene variants that cause MVID. Here, we have reviewed these patterns and correlations, which are expected to be valuable for healthcare professionals in managing the disease and providing personalized care for patients and their families.

Aspectos funcionais, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana / Functional, microbiological and morphological intestinal findings among human immunodeficiency virus infected children

RACIONAL: O trato gastrointestinal é freqüentemente acometido nas crianças infectadas pelo vírus da imunodeficiência humana, com importantes repercussões no seu estado nutricional e sobrevida. A maioria dos estudos relacionados a esse tema foi desenvolvida com adultos, sendo menos investigado o problema nas crianças OBJETIVOS: Estudar aspectos digestivo-absortivos, microbiológicos e morfológicos intestinais em crianças infectadas pelo vírus da imunodeficiência humana MATERIAL E MÉTODOS: Onze crianças infectadas pelo vírus da imunodeficiência humana, menores de 13 anos, pertencentes às categorias clínicas A, B ou C, divididas em dois grupos: cinco pacientes com relato atual ou recente de diarréia e seis pacientes sem diarréia nos 30 dias que antecederam à inclusão no estudo. Investigação proposta: biopsia de intestino delgado e reto para análise morfológica e microbiológica, coprocultura, protoparasitológico de fezes, pesquisa de rotavírus, micobactérias e Cryptosporidium; teste da D-xilose RESULTADOS: Todos os pacientes testados (9/11) apresentavam má absorção da D-xilose (8,4-24,4 mg/dL). Os achados histopatológicos de intestino delgado foram inespecíficos, representados em sua maioria, por enteropatia grau I a II (6/10). Em todos os casos foi constatado aumento do infiltrado celular do córion. As alterações histopatológicas do reto também foram inespecíficas, com presença de aumento do infiltrado celular do córion. A pesquisa de microorganismos enteropatogênicos só foi positiva em dois casos, sendo identificado Mycobacterium avium intracellulare e Cryptosporidium nas fezes CONCLUSÕES: Demonstrou-se alta prevalência (100 por cento) de má absorção intestinal em crianças infectadas pelo vírus da imunodeficiência humana, com ou sem diarréia. Não foi possível estabelecer correlações quanto à presença de agentes enteropatogênicos, má absorção intestinal, alterações morfológicas intestinais e ocorrência ou não de diarréia. Não houve correlação...

BACKGROUD: Gastrointestinal tract disorders are frequent among human immunodeficiency virus infected children, with important repercussions on nutrition and survival. Most studies related to this subject were restricted to adults, being less investigated the problem in the children. AIMS: To study intestinal digestion, absorption, microbiological and morphological findings among human immunodeficiency virus infected children. MATERIAL AND METHODS: Eleven human immunodeficiency virus infected children under 13 years old, belonging to clinical categories A, B or C, separated in two groups: five patients with current or recent episode of diarrhea and six patients without diarrhea in the last 30 days preceding entering in study. Investigation proposed: microbiological and morphological analysis of small intestine and rectum biopsy; stool exams for bacterium, parasite, rotavirus, Mycobacterium species and Cryptosporidium; D-xylose test RESULTS: All tested subjects (9/11) had low D-xylose absorption (8,4 _ 24,4 mg d/L). Small intestinal mucosa histology findings were nonspecific, represented, in majority, of grade I/II enteropathy (6/10). Increased cellular infiltration of the chorion was observed in all specimens. Rectum histology alterations were also nonspecific, with chorion increased cellular infiltration. Mycobacterim avium intracellulare and Cryptosporidium were the solely microorganisms founded, both in stool CONCLUSIONS: Our study demonstrated high prevalence (100 percent) of intestinal malabsorption among human immunodeficiency virus infected children, despite the occurrence or not of diarrhea. It was not possible to establish relationships between the presence of microorganisms, intestinal malabsorption, intestinal morphologic findings and the occurrence or not of diarrhea. There was no correlation between D-xylose and intensity of villous atrophy.

Amiloidosis, Comunicación de 11 casos y revisión de la literatura / Clinical features of patients with the pathological diagnosis of amyloidosis

Background: Amyloidosis is characterized by the extracellular deposit of an insoluble fibrillar protein that leads to tissue atrophy and necrosis. Aim: To report the clinical features of cases of amyloidosis diagnosed in a public hospital in Santiago, Chile, from 2000 to 2004. Material and methods: Retrospective review of all pathology reports of biopsies obtained from 2000 to 2004. In all cases reported as "amyloidosis", the clinical features of such patients were obtained from their medical records. Results: The medical records of 11 patients with amyloidosis were obtained (aged 35 to 71 year old, seven females). Seven had a systemic and four a localized disease. Six patients had primary amyloidosis and in one, it was secondary to a disseminated tuberculosis. Five patients with the generalized disease consulted for anarsarca, three for weight loss and 2 for chronic diarrhea. Patients with localized disease consulted for tonsil enlargement, dysphonia and skin lesions. Five patients with generalized disease had renal involvement and five had cardiac involvement. Three patients had malabsorption. Conclusions: The most common presentation of systemic amyloidosis is anasarca and renal involvement is common.

Historia de las manifestaciones gastrointestinales del lupus eritematoso sistemico / History of the gastrointestinal manifestations in systemic lupus erythematosus

En este articulo revisamos la historia de las manifestaciones gastrointestinales en el Lupus Eritematoso Sistemico desde el siglo XIX hasta nuestros dias, recorriendo cada uno de los organos involucrados en este sistema y haciendo especial mencion de la gastropatia, enteritis, ileitis, sindrome de malabsorcion, vasculitis y vasculopatia intestinal, trombosis mesenterica, pancreatitis, ascitis, peritonitis, hepatitis autoinmune, entre otros

Suplementación de DL-Ó-tocoferol acetato oral en niños con colestasis crónica y déficit de vitamina E / Supplement of Oral DL-Ó-Tocopherol Acetate in children with chronic cholestasis and vitamin E deficit

Objetivo. Determinar la dosis oral suplementaria de dl-Ó-tocoferol acetato para mantener niveles séricos de Ó-tocoferol normales en niños con colestasis crónicas y déficit de vitamina E. Antecedentes. La malabsorción y deficiencia de vitamina E en niños con colestasis crónica se presenta en un 60-70 por ciento, causando un síndrome de degeneración neurológica progresiva entre 18 y 24 meses si no se corrige. La pronta suplementación con vitamina E determina la prevención e irreversibilidad de dicho déficit. Método. Realizamos un estudio prospectivo, longitudinal y comparativo de 60 niños divididos en tres grupos, con déficit de vitamina E y colestasis crónica. Luego de una evaluación inicial y por 15 días, cada grupo recibió suplementación oral con 100 UI, 200 UI y 400 UI diarias de dl-Ó-tocoferol acetato, respectivamente. Fueron monitorizados los niveles séricos de Ó-tocoferol, la función neurológica y los parámetros bioquímicos durante la suplementación. Resultados. Ninguna de las dosis suplementarias orales de dl-Ó-tocoferol acetato administradas por 15 días normalizaron los niveles séricos de Ó-tocoferol (p>0.06). La función neurológica, que no encontraba alterada al inicio del estudio en ninguno de los pacientes, permaneció estable luego de los 15 días, a dosis de 100 UI, 200 UI y 400 UI, a pesar de ser seguro, no mantuvo los niveles séricos normales de Ó-tocoferol en niños con colestasis crónica y déficit de vitamina E

Antígeno nuclear de proliferación celular (PC10) en pacientes con síndrome de malabsorción: estudio comparativo con parámetros morfométricos / Proliferating cell nuclear antigen (PCNA) in patients with malabsorption syndrome: comparative study with morphometric parameters

The study of small bowel mucosa is routine in the study of patients with malabsorption. We report 16 children aged from 8 months to 6 years old (2 with giardiasis, 8 with primary malnutrition and 5 with celiac diasease) in whom a morphometric and PCNA immunostaining was performed in the small intestinal biopsy. Positively for PCNA was found in the lower portion of the crypts reaching 156 µm of heigh in patients with giardiasis, 103 µm in primary malnutrition and 182 µm in celiac dosease (p<0.01 compared to primary malnutrition). A negative and significant correlation was found between the degree of architectural disorder (expressed the mucosal index) and the proliferative portion of the crypts (expressed as the percentage of PCNA(+) crypts. We propose these methods as complements to the small bowel mucosa histopathological study in the diagnosis of celiac disease, to assess the degree of architectural disorder and the proliferative activity

Estudio morfométrico de biopsia de intestino delgado / Biopsy morphometric study of small intestine

Dentro del estudio clínico de pacientes con malabsorción intestinal se considera la alternativa de practicar una biopsia de intestino delgado. Según algunos autores, el examen histopatológico implica variabilidad interpersonal e intrapersonal, lo cual se corregiría al efectuar estudios morfométricos. En nuestro estudio se muestra el uso de instrumentos de cartografía (curvímetro y planímetro) en la medición de áreas y perímetros, más el uso de índices matemáticos que permiten reagrupar a las biopsias y pacientes en grados diversos de aplanamiento vellositario. Asimismo, los resultados permitieron sugerir tres categorías para el índice mocoso (mayor o igual que 3, de 1,6 a 2,9 y menor o igual a 1,5) y tres para el índice perímetro área (mayor o igual a 0,2 de 0,11 a 0,19 y menor o igual a 0,1), con concordancia estadísticamente significativa (coeficiente de Pearson de 0,8084). El análisis morfométrico permitió detectar pacientes en cuya biopsia el grado de alteración era superior al originalmente descrito. Finalmente, se muestra el grado de variabilidad interpersonal del examen de la biopsia con microscopía de luz convencional con valor Kappa global igual a 0,5254 (desde 0,169 para el grado atrofia parcial leve hasta 0,814 para atrofia subtotal). El interés reside en el costo de instalación y funcionamiento de esta técnica, la cual se ubica muy por debajo de los instrumentos tradicionales de morfometría digital

Biopsia endoscópica del yeyuno / Endoscopic biopsy of the jejunum

En 14 niños con síndrome de malabsorción o sospecha de Enfermedad Celíaca se tornaron una o más muestras endoscópicas para biopsias del yeyuno en el hospital de Iquique. Los exámenes fueron hechos bajo anestesia disociativa, empleando panendoscopios entándar de canal amplio y pinzas de biopsia. Se obtuvieron 113 muestras que fueron estudiadas en el Departamento de Anatomía Patológica del Hospital Dr. Luis Calvo Mackenna, comprobándose que eran adecuadas para el examen histopatológico