Enfermedad por inclusión microvellositaria como causa de diarrea congénita severa: caso clínico / Microvillous inclusion disease as a cause of severe congenital diarrhea: case report

Las diarreas congénitas son patologías graves de baja frecuencia y alta mortalidad. Se manifiestan durante los primeros días o meses de vida con severa diarrea, generando insuficiencia intestinal y dependencia de nutrición parenteral. Se debe sospechar ante un recién nacido o lactante con pérdidas masivas hidroelectrolíticas, y se diagnostican utilizando parámetros clínicos, endoscópicos, histológicos y eventualmente genéticos. El tratamiento es de soporte, con reposición hidroelectrolítica intensa y nutricional. OBJETIVO: Presentar un caso de diarrea congénita, identificada como Enfermedad por Inclusión Microvellositaria, de presentación neonatal. CASO CLÍNICO: Paciente varón edad actual 3 años, hijo de padres consanguíneos, quien debutó a los 10 días de vida con diarrea secretora severa, requiriendo ingreso a unidad de paciente crítico y nutrición parenteral permanente. Inicialmente además con síndrome de Fanconi, que luego se recupera. Se confirmó la sospecha de Enfermedad de Inclusión Microvellositaria utilizando microscopia óptica, electrónica e inmunohistoquímica. Se obtuvo una favorable evolución utilizando nutrición parenteral total (NPT) a domicilio. CONCLUSIONES: Se presenta el primer caso conocido en Chile de un paciente con diarrea congénita por inclusión microvellositaria manejado y su evolución.

Congenital diarrheas correspond to a severe and low frequency digestive disease, with a high mortality. They start a few days or months after birth, leading to intestinal insufficiency and dependence on parenteral nutrition. It must be highly suspected in newborns or infants with diarrhea and severe electrolyte disorders. The diagnosis is based on clinical, endoscopic, histologic and eventually genetic findings. Treatment is supportive with intensive correction of electrolyte imbalances as well as parenteral nutrition. OBJECTIVE: To present a case report of congenital diarrhea identified as microvillous inclusion disease presenting in the neonatal period. CASE REPORT: Male patient currently 3 years of age, son of consanguineous parents. At 10 days of age presents a severe secretory diarrhea, requiring treatment in a critical care unit and parenteral nutrition. Initially he also presented with Fanconi syndrome, which improved afterwards. The suspicion of congenital microvillous inclusion was confirmed later by optic and electronic microscopy, and inmunohistochemistry. A succesful evolution was later achieved maintaining home parenteral nutrition after discharge. CONCLUSION: We present the first known case in Chile of congenital diarrhea due to microvillous inclusión disease and his evolution.

Diagnosis of microvillous inclusion disease: a case report and literature review with significance for Oman

Microvillous Inclusion Disease [MVID] is one of the congenital diarrheal disorders [CDD] caused by genetic defects in enterocyte differentiation and polarization. Its prevalence is higher in countries with a high degree of consanguinity. It causes severe, intractable secretory diarrhea leading to permanent and definitive intestinal failure with resultant dependency on parenteral nutrition [PN]. Small bowel transplantation is the only curative treatment. The gold standard for diagnosis are the typical morphological abnormalities in small bowel biopsies on light and electron microscopy [EM]. In recent times, histochemistry and immunohistochemistry have shown sufficient diagnostic accuracy replacing EM if the facility is unavailable or EM findings are inconclusive. We describe a neonate with CDD who was diagnosed to have MVID on the duodenal biopsy by morphohistochemical and immunophenotypic methods used for the first time in Oman. By utilizing such easy and accessible diagnostic methods, a rare genetic disorder could be diagnosed with certainty and the family could be counseled accordingly. With a high degree of consanguinity in the region, the prevalence of MVID in Oman needs to be identified once these patients are diagnosed by utilizing appropriate investigations. Care of such patients necessitates improving current parenteral nutrition services and addressing the future need for small bowel transplantation [SBTx], in Oman

Atrofia vellositaria duodenal inducida por micofenolato mofetil: caso clínico / Duodenal villous atrophy associated with Mycophenolate mofetil: report of one case

Mycophenolate mofetil (MMF) is an immunosupressor agent frequently used in patients after bone marrow or solid organ transplants. The most common adverse reactions of the drug are gastrointestinal, specially diarrhea and vomiting. We report a 53-year-old male, that received a heart transplant receiving immunosuppression with cyclosporine, mycophenolate mofetil and prednisone. Six months after the transplant, the patient started with diarrhea, anorexia and weight loss. A duodenal biopsy showed villous atrophy. Celiac disease and the presence of parasites were discarded. Mycophenolate mofetil was discontinued and one week later, diarrhea subsided. Two months later the patient was asymptomatic and recovered weight. A new duodenal biopsy showed absence of villous atrophy.

Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction

T lymphocyte-mediated pathogenesis is common to a variety of enteropathies, including giardiasis, cryptosporidiosis, bacterial enteritis, celiac's disease, food anaphylaxis, and Crohn's disease. In giardiasis as well as in these other disorders, a diffuse loss of microvillous brush border, combined or not with villus atrophy, is responsible for disaccharidase insufficiencies and malabsorption of electrolytes, nutrients, and water, which ultimately cause diarrheal symptoms. Other mucosal changes may include crypt hyperplasia and increased infiltration of intra-epithelial lymphocytes. Recent studies using models of giardiasis have shed new light on the immune regulation of these abnormalities. Indeed, experiments using an athymic mouse model of infection have found that these epithelial injuries were T cell-dependent. Findings from further research indicate that that the loss of brush border surface area, reduced disaccharidase activities, and increase crypt-villus ratios are mediated by CD8+ T cells, whereas both CD8+ and CD4+ small mesenteric lymph node T cells regulate the influx of intra-epithelial lymphocytes. Future investigations need to characterize the CD8+ T cell signaling cascades that ultimately lead to epithelial injury and malfunction in giardiasis and other malabsorptive disorders of the intestine.

Daño ultraestructural del intestino medio abdominal de Lutzomyia ovallesi (Ortiz) (Diptera: Psychodidae) ocasionado por Leishmania (Leishmania) amazonensis / Ultrastrutuctural damage to the middle intestine of Lutzomyia ovallesi (Ortiz) (diptera: Psychodidae) caused by Leishmania (Leishmania) amazonensis

Se estudió el intestino medio abdominal de Lutzomyia ovallesi infectada con Leishmania (Leishmania) amazonensis. Las hembras se observaron a los siete días post- infección, utilizando microscopía de luz de alta resolución y microscopía electrónica de transmisión. Se distinguieron dos tipos de células epiteliales, células digestivas y células secretoras, en el intestino medio abdominal de L. ovallesi, tanto en los insectos controles como en flebotominos infectados. Los resultados muestran además, que L. ovallesi presentó alteraciones en la citoar-quitectura celular del intestino medio abdominal producto de la infección con L. (L.) amazonensis, observándose gran distensión del diámetro de la luz intestinal, degeneración de sus células, pérdida parcial o total de las microvellosidades y engrosamiento de la capa basal de toda la porción del intestino. Las células epiteliales presentaron degeneración vacuolar y mitocondrial y en la luz intestinal se observaron desechos epiteliales. El daño celular observado en el intestino medio abdominal de L. ovallesi, pueden tener relación con la secreción de lectinas y con la formación del gel observado, semejante a una matriz, en el lumen del intestino. Es necesario continuar los estudios para dilucidar aspectos importantes de la interrelación Leishmania-vector.

Apoptogenic effect of the lipophilic o-naphthoquinone CG 10-248 on rat hepatocytes: light and electron microscopy studies

CG 10-248 (3,4-dihydro-2,2-dimethyl-9-chloro-2H-naphtho[1,2b]pyran-5,6-dione; CG-NQ), a beta-lapachone analogue, modified the ultrastructure of rat hepatocytes, as demonstrated by light and electron microscopy. After 4 h incubation with 100 microM CG-NQ, the following effects were observed: (a) nuclear chromatin condensation; (b) chromatin fragmentation; (c) displacement of mitochondria, concentrated around the nucleus; (d) disruption or expansion of mitochondrial outer or inner membranes, respectively; (e) displacement and alteration of endoplasmic reticulum (rough and smooth); (f) decrease of microvilli; (g) blebbing of plasma membrane and production of apoptotic bodies formed by folding of plasma membrane fragments around mitochondria or peroxysomes; and (h) production of hydrogen peroxide. Expression of such effects varied according to hepatocyte samples and taken together strongly support an apoptotic action of CG-NQ dependent on reactive oxygen species.

Microvillus inclusion disease as a cause of severe protracted diarrhea in infants.

There are many etiologies responsible for severe intractable diarrhea in infancy, for instance, autoimmune enteropathy, microvillus inclusion disease, tufting enteropathy, food allergy, post-enteritis syndrome, chronic intestinal pseudo-obstruction, Hirschsprung's disease, intestinal lymphangiectasia, congenital sodium or chloride diarrhea, and congenital enzymatic deficiency. This article reports a case of microvillus inclusion disease in a Thai patient. He presented with severe intractable watery diarrhea with persistent metabolic acidosis. After extensive investigation, the diagnosis of microvillus inclusion disease was made, based on the ultrastructural findings of microvillus inclusions in the cytoplasm of the enterocyte on electron microscopic study. Various treatments were introduced to the patient without clinical improvement, including cholestyramine, metronidazole, probiotics, and octreotide. He was dependent on total parenteral nutrition and subsequently died from TPN-related complications. Even though it is a rare disease, it should be considered if an infant has chronic secretory diarrhea.

Protracted Diarrhea: Results of the Five-year Survey in a Tertiary Hospital in Korea

The syndrome of protracted diarrhea (PD) includes several diseases with diverse etiologies. This study was conducted to characterize the spectrum of causes, clinical manifestations, and the outcomes of PD. A retrospective analysis of the clinical and pathological findings was performed on 25 patients with diarrhea starting within the first 2 yr of life and a requirement of parenteral nutrition (PN). According to the intestinal histopathology, patients were classified into four groups: immune enteropathy (12 cases), lymphangiectasia (6 cases), epithelial dysplasia (5 cases), and unclassified (2 cases). All patients with epithelial dysplasia had earlier onset of diarrhea and longer duration of PN than those in the other groups. Three patients (12%) had an evidence of a familial condition. Five patients (three with microvillous inclusion disease and two with immune enteropathy) died. Sixteen patients recovered, and three (two with primary lymphangiectasia and one with microvillous inclusion disease) still had diarrhea. One patient underwent intestinal transplantation for tufting enteropathy. In conclusion, infants with PD should be referred to specialized centers where advanced diagnostic and therapeutic facilities are available, because histological analysis is critical for the diagnosis of PD, and PN or intestinal transplantation is the only therapeutic option in a subset of cases.

Salmonella 3, 10:r: toxicity in rabbit ileum and liver by light and electron microscopy.

Salmonella 3, 10:r:- (a monophasic variety of otherwise diphasic serotypes such as S. weltevreden and S. simi) Cell_free filtrate, when introduded into rabbit ligated ileal loops causes fluid exsorption, as studied 18-hr after treatment. Light microscopic histology of treated ileum shows denudation of the columnar epithelium at several places, thereby allowing the passage of the toxic principle into circulation. An important target organ, liver shows extensive centrilobular necrosis, as observed by light microscopy. Transmission electron microscopy of ileum reveals opening of membrane junctions between the adjacent cells of epithelial lining of the treated ileum at places, and focal devitalization including formation of intra-cellular membranous inclusinos. Electron microscopy of liver shows extensive damage and swelling of cytoplasmic membranes. However, the areas of darkly staining lamellae of granulated endoplasmic reticulum are also seen in stacks as will as dispersed. These studies stress that Salmonella toxic substances can cause extensive damage to intestine and liver both.