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Intestinal failure and transplantation in microvillous inclusion disease
Fracaso intestinal y trasplante en la enfermedadpor inclusiones microvellositarias
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"apellidos" => "Burgos Lizáldez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "Sarría Osés" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "M." "apellidos" => "Molina Arias" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "G." "apellidos" => "Prieto Bozano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Gastroenterología, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fracaso intestinal y trasplante en la enfermedadpor inclusiones microvellositarias" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1122 "Ancho" => 950 "Tamanyo" => 371802 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">PAS stain. Accumulation of PAS-positive material in the apical cytoplasm of enterocytes.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Microvillous inclusion disease (MVID) or congenital/familial microvillous atrophy is due to a congenital disorder of the epithelial cells of the bowel. The literature has reported multiple mutations in the MYO5B gene that encodes myosin Vb that are associated with the development of this disease. It usually manifests in the neonatal period with severe diarrhoea that persists despite fasting, with children becoming permanently dependent on parenteral nutrition (PN). Its histological features consist in the absence or altered appearance of the enterocyte brush border membrane along with the presence of characteristic microvillous inclusions. The treatment of MVID includes PN and intestinal transplantation.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Patients and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">We performed a retrospective review of the patients diagnosed with MVID in our hospital in a 15-year period (1998–2013). We analyzed epidemiological, clinical, diagnostic, treatment and patient outcome variables. Biopsy samples were collected by means of upper gastrointestinal endoscopy for diagnostic confirmation. A conventional histological examination was performed that included a haematoxylin–eosin stain (HE) and a periodic acid-Schiff stain (PAS), as well as immunohistochemical testing with anti-CD10 antibodies and electron microscopy examination. Two of the six patients underwent genetic testing for mutations in the MYO5B gene. Infectious, allergic and autoimmune aetiologies, defects in digestion, absorption and transport of nutrients and other diseases of the intestinal mucosa were ruled out in all patients.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">The onset of diarrhoea occurred within four days from birth in five patients, at a median age of 3 days (range, 3–30 days) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Three patients were male and 3 were female. Patients 2 and 3 were siblings born to consanguineous parents, and there was no blood relationship between the two parents of the remaining patients. Patient 6 was born to term, while the rest were born at 35–36 weeks of gestational age. All were born with normal weights for their gestational age. Prenatal ultrasonography had shown dilation of bowel loops in half of the patients, with no other significant findings.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">All six patients had onset with severe diarrhoea (stool volume ∼120–200<span class="elsevierStyleHsp" style=""></span>ml/kg/day) of the secretory type (sodium in stools >100<span class="elsevierStyleHsp" style=""></span>mEq/L) and with abundant mucus, which persisted despite fasting. Patient 5 developed renal complications associated with PN and severe electrolyte imbalances, and patient 6 developed intense skin itching as a prominent symptom. None of the patients could tolerate any type of enteral formula, and all required PN to prevent dehydration and metabolic acidosis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The upper gastrointestinal endoscopy did not show significant macroscopic abnormalities. The diagnosis was made by the histological examination of duodenal biopsies with light and electron microscopy. The presence of mutations in the MYO5B gene was confirmed in patients 5 and 6. The rest of the patients did not undergo genetic testing. All patients received PN in the hospital and at home for prolonged periods of time (3–36 months). Three of the six patients have died (one at age 3 months of septic shock, and the other two of liver complications associated with intestinal failure while they were on the transplant list). Of the three survivors, one is awaiting a multivisceral transplantation and has developed acute postinfectious glomerulonephritis, and the other two have undergone transplantation (one an intestinal transplantation and the other a combined liver and intestinal transplantation, 15 and 11 years ago, respectively), and have achieved intestinal autonomy and a good quality of life.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">There are different causes of congenital diarrhoea with onset in the early months of life: defects in the digestion, absorption and transport of nutrients and electrolytes, defects of enterocyte differentiation and polarization, defects of enteroendocrine cells differentiation and defects in the modulation of the intestinal immune response.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> Chief among the congenital enterocyte disorders are intestinal epithelial dysplasia and MVID, which are rare causes of permanent intestinal failure.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Microvillus inclusion disease, also known as congenital microvillus atrophy, was first described by Davidson et al. in five patients in 1978,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a> and the term MVID was proposed by Cutz et al. in 1989.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a> It is a congenital disease that has been recently associated in the literature with mutations in the MYO5B gene of chromosome 18 that result in the altered expression of myosin Vb in enterocytes.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4–7</span></a> Myosin Vb is a protein that binds with Rab proteins to provide the molecular basis for the regulation of recycling endosome pathways and their transport along actin filaments to the apical membrane in polarized epithelial cells. Homozygous as well as heterozygous mutations have been characterized that can cause MVID.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4–7</span></a> The exact genetic alteration was not known until 2008.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4,5</span></a> Different mutations in the MYO5B gene have since been described, with up to 41 reported until the present date.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> The two most recent patients in our series underwent genetic analysis of the MYO5B gene, and two heterozygous mutations were detected in each: the mutations c.3190C>T (p.R1064X) and c.3514C>T (p.Q1172X) in patient 5, and c.445C>T (p.Q149X) and c.5383C>T (p.R1795X) in patient 6. The patients that had been diagnosed before did not undergo genetic testing.</p><p id="par0040" class="elsevierStylePara elsevierViewall">There are patients with MVID in whom testing has not revealed mutations in the MYO5B gene. Very recently, whole-exome sequencing of DNA from patients with MVID has shown homozygous mutations in syntaxin 3 in some.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">9</span></a> Syntaxin 3 is a receptor involved in the membrane fusion of apical vesicles in enterocytes, and mutations result in their defective fusion with the apical membrane. It has been proposed that this is an atypical MVID variant, with a milder phenotype, a delayed onset, greater tolerance of enteral nutrition and subtle histological differences.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">10</span></a> Still, more studies are needed to properly establish a correlation between different mutations and phenotypical expression.</p><p id="par0045" class="elsevierStylePara elsevierViewall">During gestation, the presence of polyhydramnios and dilation of intestinal loops can be detected by ultrasonography, albeit irregularly.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> Three of our patients showed intestinal dilation without polyhydramnios in the third-trimester ultrasound. All prenatal ultrasound scans were normal in the other patients.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The disease manifests with intractable diarrhoea that usually starts in the first week of life (early-onset form) although cases with onset after weeks 6–8 of life have also been described (late-onset form).<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12–14</span></a> The diarrhoea is watery and abundant, with plenty of mucus, and can sometimes be mistaken with urine, with stool volumes of 100–200<span class="elsevierStyleHsp" style=""></span>ml/kg/day even when the patient is fasting. It leads to significant dehydration in a few hours, requiring permanent PN and high volumes of fluids and electrolytes. All our patients presented with significant weight loss and metabolic acidosis, as well as a considerable loss of sodium and chloride in stools (around 100<span class="elsevierStyleHsp" style=""></span>mmol/L and 80<span class="elsevierStyleHsp" style=""></span>mmol/L, respectively). Patient 5 was transferred from another hospital with a tentative diagnosis of enterovesical fistula based on the stool characteristics.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Historically, it was believed that MVID was not usually associated with other extraintestinal malformations, but some authors have described a co-occurrence in some of their patients of heart malformations, Down syndrome, neuronal dysplasia, hypochondroplasia or sensory deficits among others.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">14–19</span></a> Despite the widespread expression of the MYO5B gene in all epithelial tissues, it is not clear how organs other than the intestine may be affected by this disease. There has been evidence in recent years that extraintestinal manifestations are not as rare as initially thought. A recently published series of 24 patients with MVID followed up at ages ranging from birth to age 23.5 years (median duration of followup, 4.7 years) found liver disease in 22 patients, kidney disease in nine, and pulmonary disease in two.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Liver diseases, such as cholestasis, cholelithiasis and liver fibrosis, may result from prolonged PN. However, slightly elevated or normal levels of gamma-glutamyl transpeptidase (GGT) indicate that NP cannot be the sole cause of liver dysfunction. A specific form of liver disease associated to MVID has been described that is characterized by normal GGT levels and is similar to progressive familial intrahepatic cholestasis (PFIC).<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> Myosin Vb is needed for bile canalicular formation and also for the trafficking of ATP-binding-cassette transporters.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> In a study of a cohort of 28 patients with MVID of whom 8 developed cholestasis either pre or post transplant and with clinical and laboratory findings similar to those of PFIC, Girard et al. concluded that cholestasis in these patients could result from impairment of the MYO5B/RAB11A apical recycling endosome pathway in hepatocytes, altered targeting of bile salt export pumps (BSEPs) to the canalicular membrane, and increased ileal bile acid absorption.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> It is not known why not all patients develop cholestasis. Patient 6 in our series had significant cholestasis for 9 months that manifested with intense cutaneous itching and normal GGT levels. A liver biopsy of the patient did not show significant histological abnormalities, and immunohistochemical testing ruled out a BSEP and a MDR3 deficiency. The cholestasis has since resolved and the patient is now a candidate for multivisceral transplantation. It has been proposed that patients that have had liver involvement pre transplantation undergo a combined liver and intestinal transplantation to avoid the development of cholestatic diseases in the future.</p><p id="par0065" class="elsevierStylePara elsevierViewall">An association with kidney symptoms, such as haematuria or Fanconi syndrome, has also been described, <a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> as well as with endocrine conditions like diabetes.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">23</span></a> Patient 5 developed nephrocalcinosis, lithiasis and haematuria, and patient 6 acute postinfectious hypocomplementemic glomerulonephritis.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The diagnosis of MVID is made by finding the histological features characteristic of the disease in a duodenal or jejunal biopsy specimen. While light microscopy can guide the diagnosis, the definitive diagnosis requires electron microscopy.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">24,25</span></a> The histological abnormalities may be found in the colon<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> as well as the gastric mucosa.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> The presence of mutations in the MYO5B gene completes the diagnosis.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Light microscopy shows varying degrees of atrophy of the brush border microvilli, no significant signs of an inflammatory response and a normal or slightly increased density of the crypts. In healthy subjects, alkaline phosphatase<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> and PAS staining only stain the brush border of the enterocyte, while in patients with MVID the border is either not stained or is stained unevenly and there is an accumulation of PAS-positive materials in the apical cytoplasm of enterocytes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This can also be observed by means of CD10<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) and carcinoembryonic antigen immunostaining.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a> The three key ultrastructural findings include the reduction, absence and/or disorganization of microvilli in mature enterocytes; the accumulation in the apical cytoplasm, and especially of crypt cells, of secretory granules; and the characteristic intracytoplasmic inclusion bodies lined with microvilli (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). However, it is not always easy to make a histopathological diagnosis of MVID due to the existence of variants, different clinical manifestations and even a small percentage of patients in whom the typical inclusion bodies cannot be detected. In 1994 Raafat et al.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> described three children with microvillous dystrophy, a condition they considered a clinicopathologic variant of MVID that has since been addressed by other authors.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> This ultrastructural lesion was observed in patient 1 (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Disease progression invariably results in the need for PN, since enteral nutrition is not possible due to the large intestinal losses that carry the risk of dehydration and death.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Pharmacological treatment has been attempted with various agents, such as loperamide, somatostatin, corticosteroids or growth factors, among others, but none of them were efficacious in these patients.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30,31</span></a> Intestinal transplantation is currently the only option available to patients with permanent intestinal failure, especially those experiencing difficulties in the administration of PN (loss of venous access due to deep vein thrombosis) or severe complications from PN (liver disease, sepsis secondary to the presence of a central line, etc.).<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19,32,33</span></a> Two of our patients received transplants and had favourable outcomes; they have achieved intestinal autonomy and have not experienced complications associated with their underlying disease. A third patient is waiting for a multivisceral transplantation, although at present he has been temporarily removed from the transplant list due to glomerulonephritis.</p><p id="par0090" class="elsevierStylePara elsevierViewall">There have been isolated cases in the literature in which the disease improved and the patient achieved intestinal autonomy and could discontinue PN.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16,34</span></a> In a recent review of 8 cases of MVID with atypical manifestations (delayed onset and smaller diarrhoea volumes), Perry et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> described 3 cases with favourable outcomes that allowed the discontinuation of PN. In light of this, they proposed expanding the clinical spectrum of this disease to include patients with milder forms, which entails that MVID should be considered in the differential diagnosis of intractable diarrhoea beyond the neonatal period.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The most common causes of death are severe metabolic decompensation or complications from PN (liver disease or sepsis), as occurred in the three patients that died in our series.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In brief, MVID is a severe inherited genetic disease that causes early intestinal failure dependent on PN and can only be cured with an intestinal transplant. It is diagnosed on the basis of clinical, histological, ultrastructural and genetic findings, but diagnosis may be complicated in cases with atypical presentations or with an incomplete clinical picture. A differential diagnosis must be made to rule out other causes of early-onset severe diarrhoea.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres576228" "titulo" => "Abstract" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec592875" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres576229" "titulo" => "Resumen" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Resultados" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec592876" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-10-23" "fechaAceptado" => "2014-11-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec592875" "palabras" => array:5 [ 0 => "Microvillus inclusion disease" 1 => "Microvillus dystrophy" 2 => "Intestinal failure" 3 => "Intestinal transplantation" 4 => "Parenteral nutrition" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec592876" "palabras" => array:5 [ 0 => "Enfermedad por inclusiones microvellositarias" 1 => "Distrofia microvellositaria" 2 => "Fracaso intestinal" 3 => "Trasplante intestinal" 4 => "Nutrición parenteral" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Microvillous inclusion disease is a rare autosomal recessive condition, characterized by severe secretory diarrhoea that produces a permanent intestinal failure and dependency on parenteral nutrition. It usually begins in the neonatal period, and the only treatment at present is intestinal transplantation.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective review was conducted on 6 patients (three males and three females) diagnosed with microvillous inclusion disease between 1998 and 2013.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All debuted in the first month of life, with a median age of three days (range, 3–30 days), and had secretory diarrhoea dependent on parenteral nutrition, with fasting faecal volume of 150–200<span class="elsevierStyleHsp" style=""></span>ml/kg/day. Light microscopy of duodenal biopsy samples showed varying degrees of villous atrophy without cryptic hyperplasia, accumulation of PAS positive material in the cytoplasm of enterocytes brush border, and anti-CD10 immunostaining was suggestive of intracytoplasmic inclusions. Diagnostic confirmation was performed with electron microscopy. Two of them had a genetic study, and showed mutations in MYO5B gene. Three died and three are alive; two of them with an intestinal transplantation and the third waiting for a multivisceral transplantation.</p></span>" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducción</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La enfermedad por inclusiones microvellositarias es una entidad rara, de herencia autosómica recesiva y caracterizada por una diarrea grave de carácter secretor que produce un fracaso intestinal permanente dependiente de nutrición parenteral. Habitualmente se inicia en el período neonatal y el único tratamiento posible en el momento actual es el trasplante intestinal.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pacientes y métodos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Se revisa, de forma retrospectiva, a 6 pacientes (3 varones y 3 mujeres), diagnosticados entre 1998 y 2013 de enfermedad por inclusiones microvellositarias.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Resultados</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Todos comenzaron en el primer mes de vida, con una mediana de edad de tres días (rango: 3-30 días) y presentaron diarrea secretora dependiente de nutrición parenteral, con un volumen faecal en ayunas de 150-200<span class="elsevierStyleHsp" style=""></span>ml/kg/día. La microscopia óptica de muestras biópsicas duodenales mostró grados variables de atrofia vellositaria sin hiperplasia críptica, con acumulación de material PAS positivo en el citoplasma de los enterocitos del borde en cepillo y la inmunotinción anti-CD10 fue indicativa de inclusiones intracitoplasmáticas. La confirmación diagnóstica se realizó con microscopia electrónica. En 2 de ellos se realizó estudio genético que demostró mutaciones en el gen MYO5B. Evolutivamente, 3 fallecieron y 3 se encuentran vivos; 2 de ellos portadores de trasplante intestinal y el tercero en espera de trasplante multivisceral.</p></span>" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Resultados" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Fernández Caamaño B, Quiles Blanco MJ, Fernández Tomé L, Burgos Lizáldez E, Sarría Osés J, Molina Arias M, et al. Fracaso intestinal y trasplante en la enfermedadpor inclusiones microvellositarias. An Pediatr (Barc). 2015;83:160–165.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1122 "Ancho" => 950 "Tamanyo" => 371802 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">PAS stain. Accumulation of PAS-positive material in the apical cytoplasm of enterocytes.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 749 "Ancho" => 995 "Tamanyo" => 191436 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Anti-CD10 immunostain. Deep staining of the cytoplasm of brush border enterocytes.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 764 "Ancho" => 995 "Tamanyo" => 216788 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Electron microscopy. Microvillous inclusion bodies.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 613 "Ancho" => 995 "Tamanyo" => 117790 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Electron microscopy. Microvillous dystrophy. Inclusion bodies.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">F, female; GA, gestational age; ITx: intestinal transplantation; LITx, liver and intestinal transplantation; M, male; NP, not performed.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Prenatal ultrasound \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bowel dilation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bowel dilation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bowel dilation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Birth weight (g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2980 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2590 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2660 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2555 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2320 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3680 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GA (weeks) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Consanguinity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age at onset (days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stool volume (ml/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90–120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">200–300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150–200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150–200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">200 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Faecal Na (mEq/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">112.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">116.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">106.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">113.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">104.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Faecal Na/K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Extraintestinal manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nephrocalcinosis, renal lithiasis, haematuria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cholestasis, glomerulonephritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MYO5B Mutation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Outcome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AliveITx15 age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Died of sepsis (4 months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AliveLITx11 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Died while on Tx list (16 months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Died while on Tx list (29 months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AliveIn multivisceral Tx list \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab940451.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">General characteristics of patients with microvillous inclusion disease.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0175" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Congenital diarrheal disorders: an updated diagnostic approach" "autores" => array:1 [ 0 => array:2 [ "etal" => true 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 8 | 14 |
| 2024 October | 43 | 45 | 88 |
| 2024 September | 56 | 22 | 78 |
| 2024 August | 76 | 60 | 136 |
| 2024 July | 68 | 48 | 116 |
| 2024 June | 55 | 34 | 89 |
| 2024 May | 68 | 47 | 115 |
| 2024 April | 52 | 35 | 87 |
| 2024 March | 50 | 30 | 80 |
| 2024 February | 41 | 24 | 65 |
| 2024 January | 33 | 20 | 53 |
| 2023 December | 63 | 22 | 85 |
| 2023 November | 66 | 23 | 89 |
| 2023 October | 54 | 24 | 78 |
| 2023 September | 41 | 26 | 67 |
| 2023 August | 37 | 15 | 52 |
| 2023 July | 38 | 17 | 55 |
| 2023 June | 77 | 34 | 111 |
| 2023 May | 79 | 23 | 102 |
| 2023 April | 37 | 13 | 50 |
| 2023 March | 73 | 26 | 99 |
| 2023 February | 49 | 20 | 69 |
| 2023 January | 54 | 34 | 88 |
| 2022 December | 85 | 26 | 111 |
| 2022 November | 56 | 34 | 90 |
| 2022 October | 86 | 46 | 132 |
| 2022 September | 70 | 29 | 99 |
| 2022 August | 59 | 55 | 114 |
| 2022 July | 49 | 43 | 92 |
| 2022 June | 64 | 39 | 103 |
| 2022 May | 63 | 28 | 91 |
| 2022 April | 53 | 43 | 96 |
| 2022 March | 64 | 61 | 125 |
| 2022 February | 55 | 31 | 86 |
| 2022 January | 66 | 46 | 112 |
| 2021 December | 51 | 56 | 107 |
| 2021 November | 53 | 46 | 99 |
| 2021 October | 78 | 61 | 139 |
| 2021 September | 60 | 43 | 103 |
| 2021 August | 70 | 32 | 102 |
| 2021 July | 60 | 26 | 86 |
| 2021 June | 58 | 42 | 100 |
| 2021 May | 80 | 32 | 112 |
| 2021 April | 142 | 78 | 220 |
| 2021 March | 69 | 34 | 103 |
| 2021 February | 47 | 22 | 69 |
| 2021 January | 47 | 23 | 70 |
| 2020 December | 74 | 25 | 99 |
| 2020 November | 47 | 18 | 65 |
| 2020 October | 51 | 21 | 72 |
| 2020 September | 39 | 21 | 60 |
| 2020 August | 59 | 22 | 81 |
| 2020 July | 37 | 31 | 68 |
| 2020 June | 58 | 24 | 82 |
| 2020 May | 55 | 22 | 77 |
| 2020 April | 30 | 17 | 47 |
| 2020 March | 51 | 16 | 67 |
| 2020 February | 47 | 18 | 65 |
| 2020 January | 41 | 16 | 57 |
| 2019 December | 45 | 18 | 63 |
| 2019 November | 44 | 18 | 62 |
| 2019 October | 31 | 9 | 40 |
| 2019 September | 1129 | 11 | 1140 |
| 2019 August | 28 | 15 | 43 |
| 2019 July | 41 | 21 | 62 |
| 2019 June | 32 | 19 | 51 |
| 2019 May | 34 | 27 | 61 |
| 2019 April | 71 | 62 | 133 |
| 2019 March | 35 | 15 | 50 |
| 2019 February | 42 | 25 | 67 |
| 2019 January | 38 | 25 | 63 |
| 2018 December | 35 | 33 | 68 |
| 2018 November | 97 | 43 | 140 |
| 2018 October | 112 | 27 | 139 |
| 2018 September | 50 | 19 | 69 |
| 2018 June | 3 | 0 | 3 |
| 2018 May | 3 | 0 | 3 |
| 2018 April | 21 | 0 | 21 |
| 2018 March | 18 | 0 | 18 |
| 2018 February | 7 | 0 | 7 |
| 2018 January | 19 | 0 | 19 |
| 2017 December | 9 | 0 | 9 |
| 2017 November | 15 | 0 | 15 |
| 2017 October | 12 | 0 | 12 |
| 2017 September | 16 | 0 | 16 |
| 2017 August | 10 | 0 | 10 |
| 2017 July | 19 | 0 | 19 |
| 2017 June | 27 | 21 | 48 |
| 2017 May | 21 | 10 | 31 |
| 2017 April | 22 | 6 | 28 |
| 2017 March | 13 | 35 | 48 |
| 2017 February | 7 | 7 | 14 |
| 2017 January | 14 | 5 | 19 |
| 2016 December | 29 | 13 | 42 |
| 2016 November | 29 | 9 | 38 |
| 2016 October | 34 | 17 | 51 |
| 2016 September | 37 | 8 | 45 |
| 2016 August | 32 | 7 | 39 |
| 2016 July | 16 | 14 | 30 |
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