DOI: 10.1542/peds.2011-0937; originally published online January 23, 2012;PediatricsPapaioannou and Christos Bartsocas

Aglaia Zellos, Diagoras Zarganis, Stelios Ypsiladis, Dimitris Chatzis, GeorgiaEnteropathy in Infancy

Malrotation of the Intestine and Chronic Volvulus as a Cause of Protein-Losing  

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Malrotation of the Intestine and Chronic Volvulus asa Cause of Protein-Losing Enteropathy in Infancy

abstractProtein-losing enteropathy in children is caused by intestinal meta-bolic, inflammatory, or infectious processes, or by lymphatic obstruc-tion (intestinal lymphangiectasia). In this report, a 17-month-old childis presented with protein-losing enteropathy due to intestinal malro-tation and chronic midgut volvulus causing lymphatic obstruction andspillage of lymph in the intestine and the peritoneum. This reportshould alert the pediatrician that intestinal malrotation should beadded to the wide list of possible causes of protein-losing enteropathyin children. Pediatrics 2012;129:515–518

AUTHORS: Aglaia Zellos, MD,a,b Diagoras Zarganis, MD,b

Stelios Ypsiladis, MD,b Dimitris Chatzis, MD,a,b GeorgiaPapaioannou, MD,c and Christos Bartsocas, MDb

aFirst Department of Pediatrics, University of Athens School ofMedicine, Athens, Greece; bDepartment of Pediatrics, MiteraChildren’s Hospital, Athens, Greece; and cDepartment ofRadiology, Mitera Children’s Hospital, Athens, Greece

KEY WORDSchildren, chronic midgut volvulus, intestinal malrotation, protein-losing enteropathy

ABBREVIATIONSIgA—immunoglobulin AIgE—immunoglobulin EIgG—immunoglobulin GIgM—immunoglobulin MMRA—magnetic resonance angiographyPLE—protein-losing enteropathyUGI—upper gastrointestinal

Dr Zellos is the first author and wrote the paper and collectedand interpreted the data. Drs Zellos and Bartsocas were theattending physicians responsible for the patient in this casereport. Drs Zarganis, Ypsiladis (the operating surgeon),Papaioannou, Chatzis, and Bartsocas participated in the clinicalcare of the patient, assisted in editing the draft. In addition, DrsYpsiladis and Papaioannou provided all the images. All authorshave participated in the concept and design, analysis andinterpretation of data, drafting or revising of the manuscript,and they have approved the manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2011-0937

doi:10.1542/peds.2011-0937

Accepted for publication Sep 16, 2011

Address correspondence to Aglaia Zellos, MD, First Department ofPediatrics, University of Athens School of Medicine, Aghia SophiaChildren’s Hospital, Thivon and Levadias Street, Athens, Greece11527. E-mail: eglie1@aol.com, azellos@otenet.gr

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

PEDIATRICS Volume 129, Number 2, February 2012 e515

CASE REPORT

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Protein-losing enteropathy (PLE) is a clin-ical entity defined by abnormal proteinloss from thedigestive tract resulting indecreased concentration of serum pro-teins such as albumin, a1-antitrypsin,ceruloplasmin, fibrinogen, transferrin,and hormone-binding proteins withconcomitant hypogammaglobulinemiaand lymphocytopenia.1 PLE in childrenis caused by intestinal metabolic, inflam-matory, or infectious processes, or byprimary or secondary lymphatic obstruc-tion (intestinal lymphangiectasia).1,2 Inthis report, a 17-month-old child withPLE caused by intestinal malrotationand chronic midgut volvulus, resultingin lymphatic obstruction and spillageof lymph in the peritoneum in the ab-sence of bilious vomiting, is presented.Thus, intestinal malrotation should beadded to the differential diagnosis ofPLE in infancy and childhood.

CASE REPORT

A 17-month-old boy from Albania wasadmitted to our hospital with hypo-albuminemia, peripheral edema, di-arrhea, and failure to thrive since 9months of age. At age 3 weeks, he de-veloped bilious vomiting caused byjejunal duplication diagnosed by lapa-rotomy and resected without compli-cations in his home country. He wasexclusively breastfed up to 12 monthswhen cow’s milk supplementation wasadded. Solids and gluten were in-troduced gradually at 6 months. Hisgrowth up to 9 months of age wasnormal. At age 9 months, he developedwatery diarrhea and poor weight gainthat resulted in multiple hospital-izations. Although stool cultures werenegative for bacteria and parasites, hereceived a 15-day course of oral met-ronidazole for presumed giardiasiswithout improvement. Because pediat-ric endoscopy was unavailable in hiscountry, he was treated empirically withalbumin infusions, antiplasmin therapywith trans-4-aminothylcyclohexaminecarboxylic acid (tranexamic acid) and 1

mg/kg daily prednisone for 1 monthwithout discernible improvement. Atpresentation to our hospital, his weightwas 9.0 kg (less than the third per-centile for age), his height was 78 cm(less than the third percentile for age),and his head circumference was 46.5cm (less than the third percentile forage). He had facial and peripheral ex-tremity edema. The cardiac and re-spiratory systems were normal. Theabdomen was nontender and mildlydistended with hyperactive bowelsounds, without hepatosplenomegalyor ascites. Laboratory tests revealedthe following values: serum albuminwas 2.2 g/dL, total protein 4.5 mg/dL, se-rum glutamic oxaloacetic transaminase47 U/L, serum glutamic pyruvate trans-aminase 38 U/L, g-glutamyltransferase20 U/L, alkaline phosphatase 117 U/L,cholesterol 144 mg/dL, triglycerides 60mg/dL. His white blood cell count was16 130/mL, with marked lymphopeniaof 11%. His platelet count was 828 000/mL, hemoglobin level was 15.8 g/dL,and hematocrit level was 47.6%. Se-rum immunoglobulins IgG, IgM, and IgAwere all decreased. Serum IgE levelwas 12 IU/mL (normal for age ,49). Aurinalysis did not reveal proteinuria.Serology results for systemic lupuserythematosus were negative. The re-sults of a cardiac echogram and achest x-ray were normal. There waselevated stool a1-antitrypsin. The re-sults of stool cultures for known patho-gens and parasites were negative. Theprednisone dose was gradually de-creased and stopped. An upper gas-trointestinal (UGI) endoscopy excludedMenetrier disease, Helicobacter pylorigastritis, and celiac disease. Therewere no signs of intestinal lym-phangectasia or duodenal villous at-rophy, but eosinophilic duodenitis wasnoted with an eosinophil count in thelamina propria of 35per high-powerfield. Colonoscopy excluded inflam-matory bowel disease. Skin prick andatopy patch testing showed allergy to

milk, wheat, oats, bananas, and pears.For the next 2 weeks, he receiveda diet without these food antigensand a hypoallergenic milk formulawith medium-chain triglycerides; hisdiarrhea improved, but his serum al-bumin remained low. A 99mTc humanserum albumin scan showed diffuseloss of albumin in the colon and ex-cluded a focal leakage related toprevious surgical resection (blindloop). An abdominal ultrasound wasperformed but was not diagnostic be-cause of increased bowel gas. Sub-sequently, a MRI of the abdomen wasordered to exclude a retroperitonealmass causing lymphatic system ob-struction. Computed tomography wasavoided for reasons of radiation pro-tection in this multiply hospitalizedchild. Apart from extended mesentericedema, appearances of whirlpool signwere noted in the superior mesentericvessel branches which became moreconspicuous in the additionally per-formed magnetic resonance angiogra-phy (MRA) (Fig 1). The latter emphasizeda relevant dilatation of the superiormesenteric vein branches, which couldexplain both the mesenteric edema andthe clinical manifestations of venous“obstruction.” In addition, MRA sug-gested incomplete vascular volvulus.Differential diagnosis included malro-tation of the intestine or acquired non-complete small-bowel volvulus. A UGIcontrast study confirmed this finding,because the duodenum was dilated,the jejunum was partially obstructed,and the ligament of Treitz was locatedin the right side of the abdomen. Dur-ing laparotomy, chronic midgut volvu-lus was found with 180° twisting of thejejunum and the superior mesentericvessels (Fig 2) causing lymphatic ob-struction and spillage of milky whitelymph into the cut surfaces of themesentery. The mesenteric lymphnodeswere enlarged, and there was nobowel ischemia. No signs of previoussurgery were found, with the exception

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of an appendectomy. The volvulus wasuntwisted, the Ladd bands were resec-ted, and the ligament of Treitz was mo-bilized. After surgery, the child’s serumalbumin concentration gradually in-creased to normal levels and remainedstable 6 months after the operation. Heremains on hypoallergenic diet pendingreevaluation by the allergist.

DISCUSSION

PLE is a rare condition characterized byprotein loss from the gastrointestinaltract presenting at any age from theneonatal period into adolescence.Children with PLE typically presentwith facial, palpebral, or peripheraledema and diarrhea, and laboratoryinvestigations show lymphopenia,serum hypoalbuminemia, and hypo-gammaglobulinemia, rendering themvulnerable to infections. Table 1 presentsthe variety of known-to-date disorders

that should be considered by the pedi-atrician when faced with a child withsuspected PLE.1–11 Two surgical casereports published in the 1980s12,13 in-dicated that intestinal malrotationcaused PLE in two Japanese infants, yetthis diagnosis has not been included inprevious reviews on PLE in children.1,2

In this report, we presented yet an-other case of chronic midgut volvuluscausing PLE in a child, in the absence ofbilious emesis and abdominal pain.

After PLE is diagnosedby increased fecala1-antitrypsin clearance, renal proteinloss, cardiac disorders, and liver dis-orders should be excluded. Bacterial,viral, and parasitic infections should beconsidered.14 Esophageal, gastric, andintestinal mucosal pathology should beexamined by endoscopy. UGI endoscopyand colonoscopy are essential in rulingout all causes of mucosal inflammationas listed in Table 1, and biopsies shouldbe obtained from all anatomic sites.Occasionally, as in our case, the duo-denal biopsies may not identify intesti-nal lymphangiectasia, especially if notpreceded by a fatty meal. Recently, wire-less capsule endoscopy and double-balloon enteroscopy have been usefulin detecting sites of chylous leakage inthe more distal parts of the smallbowel not reached by UGI endoscopy,the latter allowing for diagnostic bi-opsies.15 A UGI contrast study may helpidentify hypertrophic gastritis, in-testinal malrotation, and intestinal

blind loops. The most commonly used99mTc human serum albumin scanmay help define abnormal lymphaticvessel anatomy and focal lymph lossinto the intestine.16 In our case, themagnetic resonance study ordered torule out a retroperitoneal mass led tothe diagnosis of malrotation andchronic midgut volvulus.

FIGURE 1A whirlpool sign was noted in the superior mesenteric vessels branches (A and B) which became moreconspicuous in the additionally performed MRA (C). The results of the MRA suggested incompletevascular volvulus and dilatation of the superiormesenteric vein branches, which could explain both themesenteric edema and the clinical manifestations of venous “obstruction.”

FIGURE 2Laparotomy image of the intestinal malrotationwith twisting 180° of the jejunum, superiormesenteric artery, and vein, causing partial in-testinal, venous, and arterial obstruction.

TABLE 1 Differential Diagnosis of Protein-Losing Enteropathy in Children

Gastrointestinal mucosal injury

1. Inflammatory bowel disease: Crohn disease andulcerative colitis

2. InfectionsBacterial: Salmonella, Shigella, Campylobacter,Clostridium difficileParasitic: Giardia lamblia, StrongyloidesstercoralisViral: rotavirus, cytomegalovirus, measles

3. Gastrointestinal tumorsEsophageal, gastric, colonic adenocarcinomasLymphoma, Burkitt lymphomaLymphangiomaKaposi sarcomaHemangiomaGastrointestinal tract involved Langerhans cellhistiocytosis

4. Juvenile polyposis5. NSAID enteropathy6. Graft versus host disease7. Post liver transplant lymphoproliferative disease8. Necrotizing enterocolitis9. Hypertrophic gastropathy (Menetrier disease)10. Eosinophilic gastroenteritis, food-induced

enteropathy11. Celiac disease12. Other intestinal: paraduodenal hernia, intestinal

stenosis, stagnant loop, small intestinalbacterial overgrowth, anastomotic ulcerationor ischemia, superior mesenteric arterydissection, and thrombosis

13. Vasculitic disorders: systemic lupuserythematosus, Henoch-Schonlein purpura

Lymphatic system abnormalities1. Primary intestinal lymphangiectasia

Congenital hypoplasia of the mesentericlymphatic system

2. Secondary intestinal lymphangiectasiaObstructive: Crohn, sarcoidosis, lymphoma,retroperitoneal tumors (neuroblastoma)Elevated lymph pressure: congestive heartfailure, pericarditis, post-Fontan procedureSyndromal: Turner, Noonan, Hennekam,Klippel-TrenaunayMetabolic: congenital disorders ofglycosylation, enterocyte heparin sulfatedeficiency, infantile sialic acid storage disease

Sources: Sylvester,1 Braamskamp et al,2 Sparks et al,3

Shima et al,4 Yamashita et al,5 Lou et.al,6 Kirchner,7 Youneset al,8 and Stormon et al.9

CASE REPORT

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Our patient presented with biliousvomiting in theneonatal periodandwasoperated on immediately for presumedsmall-bowel intestinal duplication. Theparents were not aware of any asso-ciated bowel anomalies. After the op-eration, the infant was asymptomaticuntil age 9 months when he developeddiarrhea and failure to thrive. The typ-ical findings of intestinal malrotationand volvulus, such as bloody stools,colicky abdominal pain, and biliousemesis,werenotpresent; therefore, thediagnosis was not suspected by thepediatricians. The subsequently diag-nosed eosinophilic duodenitis and foodallergy may have been triggered bychronic gut ischemia and could havecontributed to the infant’s PLE; however,a food exclusion diet did not improve

his hypoalbuminemia. Similarly, thesmall-bowel bacterial overgrowth of-ten accompanying intestinal obstruc-tion may have contributed to thischild’s symptoms; however, treatmentwith oral metronidazole did not ame-liorate his condition. Intraoperatively,the dilated lymphatic vessels and theleakage of chylous fluid into the peri-toneum clearly identified lymphaticobstruction as the etiology of PLE.

Chronic midgut volvulus is less commonthan acute volvulus, and symptoms maybe less prominent. Bilious vomiting istypical, but it may not always be pres-ent. Nonbilious vomiting may also be asymptom due to gastroduodenal dis-tention. Recurrent abdominal pain andmalnutritionare frequentpresentations.

Imamoglu et al17 presented four chil-dren with diarrhea and malabsorption-like symptoms secondary to chronicmidgut volvulus. Vascular compromisemay occur from proximal occlusion ofthe superiormesenteric vessels, but it isoften alleviated by the development ofcollaterals.18 If further twisting occurs,chronic volvulus may evolve into cata-strophic ischemia and loss of bowel.

In conclusion, intestinal malrotation andchronic midgut volvulus resulting inlymphaticandvenousobstructionshouldbe added to the differential diagnosis ofPLE in infancy and childhood. Early sus-picion and detection by the pediatricianmay prevent catastrophic bowel ische-mia and life-threatening infections, se-vere malnutrition, and lymphedema.

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2. Braamskamp MJAM, Dolman KM, TabbersMM. Clinical practice. Protein-losing enter-opathy in children. Eur J Pediatr. 2010;169(10):1179–1185

3. Sparks SE, Krasnewich DM. Congenitaldisorders of glycosylation overview. In:Pagon RA, Bird TD, Dolan CR, Stephens K,eds. GeneReviews [Internet]. Seattle, WA:University of Washington, Seattle; 1993–2005 Aug 15 [updated Sep 01, 2009]

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18. Mori H, Hayashi K, Futagawa S, Uetani M,Yanagi T, Kurosaki N. Vascular compromisein chronic volvulus with midgut malrota-tion. Pediatr Radiol. 1987;17(4):277–281

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DOI: 10.1542/peds.2011-0937; originally published online January 23, 2012;PediatricsPapaioannou and Christos Bartsocas

Aglaia Zellos, Diagoras Zarganis, Stelios Ypsiladis, Dimitris Chatzis, GeorgiaEnteropathy in Infancy

Malrotation of the Intestine and Chronic Volvulus as a Cause of Protein-Losing  

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