Challenges of microvillus inclusion disease in the nicu. Abstract microvillus inclusion disease mvid is a rare autosomal recessive disease presenting as intractable secretory diarrhea in infancy. Microvillous inclusion disease diagnosed by gastric biopsy. Pas and cd10 were performed if not available along with electron microscopic examination of the cases. Investigation before multivisceral transplantation included biopsies of the rectum, stomach, duodenum, and liver. This rare disease is characterized by lack of microvilli on the surface of enterocytes in the small intestine, the presence of pathognomonic intracellular microvillus. This means that the disease is carried by a gene on a chromosome which is not involved in determining a persons sex. Among our cohort of 28 mvid patients, 8 developed a cholestatic liver disease akin to progressive familial intrahepatic cholestasis pfic.
This is the first report of an infant with microvillus inclusion disease that presented with bowel dissection. Mvid is caused by mutations in the myo5b gene, coding for the myosin vb motor protein. Autophagocytosis of the apical membrane in microvillus. Identification of ion transport defects in microvillus inclusion disease. The intestinal biopsy is a cornerstone in the investigation of many of these patients, and the role of the pathologist can be pivotal in establishing the diagnosis. The typical pathological features of the disease are well known whereas the pathophysiology is still unclear. Villin immunohistochemistry is a reliable method for diagnosing microvillus inclusion disease. How ever, the exact pathophysiology of mv id still remains unclear. Microvillous congenital atrophy is a rare congenital disorder and it has been estimated that there were no more than a few hundred children with microvillus inclusion disease in europe. The zebrafish goosepimplesmyosin vb mutant exhibits cellular. Regina kwon, jialing huang, kiyoko oshima, mikako warren, lysandra voltaggio, ying wang, elizabeth a montgomery, danielle hutchings, microvillus inclusion disease mvid is a rare autosomal recessive disease presenting as intractable secretory diarrhea in infancy. Microvillus inclusion disease is inherited as an autosomal recessive genetic trait.
Whitington,3 and emmanuel jacquemin1,2 some patients with microvillus inclusion disease due to myosin 5b myo5b mutations may develop cholestasis char. Patients with mvid suffer from intractable diarrhea and malabsorption due to absent or very sparse microvilli and typically do not live past. Microvillus inclusion disease mvid is a rare congenital disorder that manifests early in infancy as intractable watery diarrhea. A large number of such patients eventually develop cholestatic liver disease.
Microvillous inclusion disease as a cause of severe. Microvillus inclusion disease mvid is an extremely rare inherited intestinal disorder enteropathy that is typically apparent within hours or days after birth. The congenital diarrhea of neonatal presentation means a rare and severe pathology that initially. Abnormal expression of brushborder membrane transporters in the duodenal mucosa of two patients with microvillus inclusion disease. The entity is characterized morphologically by a deficient brush.
Although myo5b gene is expressed in all epithelial tissues, it is. Incubation periods amounted to 10 minutes for biopsy specimens and 30 minutes to one hour for necropsy samples. The complete inability to absorb nutrients from intestinal lumen demands total parenteral nutrition, and, eventually. From the start of their lives, patients with mvid suffer from unstoppable secretory diarrhea at complete bowel rest that is, in the absence of enteral feeding. Transmission electron microscopy demonstrates shortening or absence of apical microvilli, pathognomonic microvillus inclusions in mature enterocytes and subapical accumulation of periodic acidschiffpositive granules or vesicles confirming diagnosis. Pantoea agglomerans, a plant pathogen causing human disease. A technique using alkaline phosphatase histochemistry on routine sections of four jejunal biopsy specimens and one necropsy sample was applied to show that alkaline phosphatase activity, normally present in the brush border, occurs in the enterocytes of patients with microvillus inclusion disease. The disorder is characterized by chronic, severe, watery diarrhea and insufficient absorption malabsorption of necessary nutrients due to incomplete development hypoplasia andor. Congenital microvillous atrophy cmva is the leading cause of neonatal. Myo5b deficient mice showed no overt defects during embryonic development, having normal size and weight.
Mutations in the myosin vb gene myo5b have been identified in the maj ority of mvid patients. Sequencing and mlpa analysis detect biallelic mutations in 90 % of patients referred with a clinical histopathologic diagnosis of mvid n 70. Microvillus inclusion disease mvid is one of the most severe congenital diarrheal diseases. Myosin 5b loss of function leads to defects in polarized signaling. Mvid manifests either in the first days of life earlyonset form or in the first two months lateonset form of life. Degeneration of their small intestine causes the patients inability to absorb nutrients from the diet and makes them lifelong dependent on intravenous feeding.
This study was performed to define possible alterations of the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in mid. Jan 25, 20 microvillus inclusion disease mvid, a rare severe congenital enteropathy characterized by intracytoplasmic microvillous inclusions and variable brush border atrophy on intestinal epithelial cells histology, is associated with defective synthesis or abnormal function of the motor protein myosin vb encoded by the myo5b gene. Patients suffer from intractable secretory diarrhea, nutrient. Microvillus inclusion disease mvid is caused by inactivating mutations in myosin vb myo5b. Microvillus inclusion disease mvid is a rare autosomal recessive. Microvillus inclusion disease mvid is one such example, arising from the inability to form and maintain microvilli at the apical cell surface aldaraji et al. Kravtsov,1 md kaimul ahsan,1 vandana kumari,1 sven c. Jul 16, 2014 microvillus inclusion disease mvid is characterized by onset of intractable lifethreatening watery diarrhea during infancy. Pdf microvillous inclusion disease mvid is one of the congenital diarrheal disorders cdd caused by genetic defects in enterocyte. Towards understanding microvillus inclusion disease molecular. Salas3 1department of pediatrics, cellular and molecular physiology, yale university school of medicine, new haven, connecticut.
New findings apical transporters nhe3, sglt1 and aqp7 were reduced in the brush borders of myo5b ko mouse enterocytes. Microvillous inclusion disease is a rare autosomal recessive condition. The diarrhea often exceeds that seen in cholerainfected children but. Microvillus inclusion disease, also known as davidsons disease, congenital microvillus atrophy and, less specifically, microvillus atrophy note. Mice with deletion of myo5b show severe secretory diarrhea similar to mvid patients, the cause for which remains unclear. Microvillus inclusion disease mvid is a rare autosomal recessive disease presenting as intractable secretory diarrhea in infancy. Microvillous inclusion disease microvillous atrophy. Towards understanding microvillus inclusion disease.
Microvillus inclusion disease mid is a disorder with the clinical signs of intractable diarrhoea in the newborn and infancy. Microvillus inclusion bodies in mid originate from autophagocytosis of the apical membrane of enterocytes with engulfing of microvilli. Microvillous inclusion disease mvid is a congenital disorder of the enterocyte related to mutations in the myo5b gene, leading to intractable diarrhea often necessitating intestinal transplantation itx. Standard histology reveals a variable degree of villous atrophy without marked crypt hyperplasia, in addition to abnormal periodicacid schiff.
Myosin 5b loss of function leads to defects in polarized. A trial of somatostatin therapy was ineffective in controlling the diarrhea. Microvillus inclusion disease variant in an infant with intractable. Kravtsov d, mashukova a, forteza r, rodriguez mm, ameen na salas pj. Neonatal congenital microvillus atrophy postgraduate medical. Unequal effects of myosin 5b mutations in liver and. Symptoms typically develop in the first days earlyonset or first months lateonset of life. Indeed, myo5b knockout mice showed all the typical features observed in patients with early onset mvid, the most common form of this disease accounting for 80% of the cases4.
Microvillus inclusion disease mvid is one of the most severe congenital. Microvillus inclusion disease mvid is an autosomal recessive syndrome affecting the intestinal epithelium. Whitington,3 and emmanuel jacquemin1,2 some patients with microvillus inclusion disease due to myosin 5b. Microvillus inclusion disease mvid is an autosomal recessive syndrome affecting the intestinal epithelium1,2. Mvid can be diagnosed based on loss of microvilli, microvillus inclusions, and accumulation of subapical vesicles. Microvillus inclusion disease surgical pathology criteria. Editing myosin vb gene to create porcine model of microvillus inclusion disease, with microvillus lined inclusions and alterations in sodium transporters. Extraintestinal manifestations in an infant with microvillus. Microvillus inclusion disease mid is a disorder within the syndrome of intractable diarrhoea of infancy. Microvillus inclusion disease is a condition characterized by chronic, watery, lifethreatening diarrhea typically beginning in the first hours to days of life. The diagnosis of this condition is based on typical light and electron microscopic em changes seen on small intestinal biopsies. Myo5b knockout mice as a model of microvillus inclusion disease. Microvillus inclusion disease mvid is a very rare and severe genetic bowel disorder that affects infants and young children. Microvillus inclusion disease mvid is an autosomal recessive disorder that presents in the neonatal period with severe secretory diarrhea and has no specific treatment and a.
Microvillus inclusion disease mvid is a congenital enteropathy characterized by loss of apical microvilli and formation of cytoplasmic inclusions lined by microvilli in enterocytes. In some cases histology of the detached bowel segment. Microvillus inclusion disease mvid is a rare intestinal enteropathy with an onset within a few days to months after birth, resulting in persistent watery diarrhea. Microvillus inclusion disease mvid is an autosomal recessive disorder that presents in the neonatal period with severe secretory diarrhea and has no specific treatment and a high mortality 2. Myo5b knockout mice as a model of microvillus inclusion. In the more common early onset form, affected patients present in the first. It was first described in 1978 and it is characterized by the onset of abundant neonatal watery diarrhea that most commonly starts within the first days of life, and can cause the loss of up to 30% of body weight within 24 h 1,2. Villin immunohistochemistry is a reliable method for. The zebrafish goosepimplesmyosin vb mutant exhibits. Microvillous inclusion disease mvid is a congenital, usually neonatal. Myo5b and bile salt export pump contribute to cholestatic. Rarely, the diarrhea starts around age 3 or 4 months.
The diagnosis of microvillus inclusion disease was established by documentation of microvillus inclusions in duodenal epithelial cells. Microvillus inclusion disease with novel myo5b pathogenic variants. The peripheral blood sample also revealed myo5b mutation. Joint transnational call 2020 kickoff meeting funded projects. Enteropathies of infancy diagnostic histopathology. Both boys and girls can be affected, although it does seem to appear in girls more often.
University of groningen pathogenic mechanisms in microvillus. Jan 29, 2016 microvillus inclusion disease mvid is characterised by onset of intractable lifethreatening watery diarrhoea during infancy. Towards understanding microvillus inclusion disease ncbi nih. Pdf congenital microvillous atrophy, report of two.
Sections were cut at 5 micron, mounted on to glass slides, and dried overnight at 37 degrees c. Small intestine autophagocytosis of the apical membrane in. In an infant with microvillus inclusion disease confirmed by electron microscopic evaluation of rectal, jejunal, and gallbladder mucosae, basal stool output was massive 125 ml kg. Gastrointestinal microvillus inclusion disease american.
Missense and nonsense mutations in the myo5b gene cause microvillus inclusion disease mvid, a congenital enteropathy characterized by loss of apical microvilli and cytoplasmic microvillus inclusion. This is seen in infections caused by epec subgroup escherichia coli, in celiac disease, and microvillus inclusion disease an inherited disease characterized by defective microvilli and presence of cytoplasmic inclusions of the cell membrane other than the apical surface. Most patients with mvid have mutations in myosin vb that cause defects in recycling of apical vesicles. Mvid is an intractable diarrhea of infantile onset with characteristic histopathologic. Small bowel small intestine microvillus inclusion disease. Myo5b mutations cause cholestasis with normal serum. An inducible mouse model for microvillus inclusion disease reveals a role for myosin vb in apical and basolateral trafficking kerstin schneebergera, georg f. Of the 21 patients with cvl infections, 8 had hematologic malignancies or bone marrow transplants, 7 had solid tumors, 3 had congenital heart disease, 1 had renal failure, 1 had necrotizing enterocolitis, and 1 had microvillus inclusion disease. Pharmacological and parenteral nutritionbased interventions. An inducible mouse model for microvillus inclusion disease. Mvid typically manifests within the first few days of life, although variable presentations have been described 1. The demonstration of alkaline phosphatase activity in routinely processed biopsy specimens provides an effective, quick, and definitive test in the diagnosis of microvillus inclusion disease without recourse to electron microscopy. Microvillus inclusion disease mvid is a severe form of congenital. Identification of intestinal ion transport defects in.
A charles, j m papadimitriou, department of pathology, university of. Myosin vb uncoupling from rab8a and rab11a elicits. Microvillus inclusion diseasemvid is a rare but lifethreat ening disease that affects newborns and children and leads to rapid death from severe secretory diarrhea. It was first described in 1978 and it is characterized by the onset of abundant neonatal watery diarrhea that most commonly starts within the first days of life, and can cause the loss of up to 30% of body weight within 24. Microvillus inclusion disease is an inherited intestinal brush border membrane defect that causes severe fluid and electrolyte malabsorption. Microvillous inclusion disease emmanuel gonzales,1,2 sarah a. The microvillus inclusion disease was described for the first time in 1978 by david andersen et al. Microvillus inclusion disease mvid is an autosomal recessive syndrome affecting the intestinal epithelium 1,2. Gastrointestinal endoscopy is usually normal, however, standard intestinal histology shows a variable degree of villous atrophy. Microvillus inclusion disease genetic and rare diseases. The entity is characterized morphologically by a deficient brush border and apical cytoplasmic inclusions within absorptive cells enterocytes due to misplaced assembly of brush border proteins. The entity is characterized morphologically by a deficient brush border and apical cytoplasmic inclusions within absorptive cells enterocytes due to. Many of the entities that cause severe enteropathy of infancy have been recognized only in the last several decades. Microvillous inclusion disease microvillous atrophy orphanet.
This pathology leads to the characteristic intractable, lifethreatening, watery diarrhea. Microvillus inclusion disease mvid is a disorder of intestinal epithelial differentiation characterized by lifethreatening intractable diarrhea. Jejunal biopsyspecimensandnecropsy samples from patients without microvillus inclusion disease servedascontrols. Diagnosis is based on intestinal biopsy demonstrating villous atrophy, crypt hypoplasia, and, on electron microscopy, microvillus inclusion. Myo5b mutations cause cholestasis with normal serum gamma. Microvillus inclusion disease is a rare and fatal congenital enteropathy, presenting with intractable secretory diarrhea shortly after birth. Oct 05, 2011 microvillus inclusion disease is an intestinal disorder characterized by severe, watery diarrhea and an inability of the intestines to absorb nutrients. C epithelial abnormalities microvillus inclusion disease tufting enteropathy c eosinophils eosinophilic gastroenteritides c absence or paucity of in. Microvillus inclusion disease, a severe malabsorption syndrome, begins at birth with intense watery diarrhea. Microvillus inclusion disease nord national organization. Microvillus inclusion disease congenital microvillus atrophy, although rare, appears to be the most common cause of congenital intractable watery diarrhea. The rab11 effectors fip5 and fip1 regulate zebrafish. However, it is not always easy to make a histopathological diagnosis of mvid due to. Jun 26, 2006 microvillous inclusion disease mvid or microvillous atrophy is a congenital disorder of the intestinal epithelial cells that presents with persistent lifethreatening watery diarrhea and is characterized by morphological enterocyte abnormalities.
Implication for microvillus inclusion disease pathogenesis and treatment. Enteropathies of infancy constitute a heterogeneous group of disorders which are difficult to diagnose and to manage. Microvillous inclusion disease mvid is a congenital, usually neonatal, autosomal recessive condition manifested by severe, prolonged secretory diarrhea. Intestinal failure and transplantation in microvillous inclusion. Ameen1,5 1department of pediatricsgastroenterology and hepatology, yale school of medicine, new haven, connecticut. Nov 03, 2015 microvillus inclusion disease mvid is a dreadful enteropathy inherited in an autosomal recessive manner and reported in infants often born of consanguineous parents. Myo5b mutations cause cholestasis with normal serum gammaglutamyl transferase activity in children without microvillous inclusion disease emmanuel gonzales,1,2 sarah a.
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