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Journal of Indian Association of Pediatric Surgeons
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Year : 2021  |  Volume : 26  |  Issue : 5  |  Page : 351-353

Protein-losing enteropathy associated with thrombotic microangiopathic features revealing hirschsprung's disease in a child

Department of Pediatrics, Child and Mother Hospital, Mohammed VI University Hospital Center, Marrakesh Medical and Pharmacy Faculty, Caddy Ayad University, Marrakesh, Morocco

Date of Submission20-May-2020
Date of Decision07-Jul-2020
Date of Acceptance18-Aug-2020
Date of Web Publication16-Sep-2021

Correspondence Address:
Prof. Houda Nassih
Department of Pediatrics, Child and Mother Hospital, Mohammed VI University Hospital Center, Marrakesh Medical and Pharmacy Faculty, Caddy Ayad University, Marrakesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaps.JIAPS_173_20

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We report the case of a 4-year-old boy with protein-losing enteropathy, leading to severe malnutrition. Associated thrombotic microangiopathic features made diagnosis difficult and challenging.

Keywords: Anemia, Hirschsprung's disease, protein-losing enteropathy, thrombocytopenia, Vitamin B12 and B9 deficiencies

How to cite this article:
Nassih H, Mahir N, Taher F, El Qadiry R. Protein-losing enteropathy associated with thrombotic microangiopathic features revealing hirschsprung's disease in a child. J Indian Assoc Pediatr Surg 2021;26:351-3

How to cite this URL:
Nassih H, Mahir N, Taher F, El Qadiry R. Protein-losing enteropathy associated with thrombotic microangiopathic features revealing hirschsprung's disease in a child. J Indian Assoc Pediatr Surg [serial online] 2021 [cited 2023 Mar 26];26:351-3. Available from: https://www.jiaps.com/text.asp?2021/26/5/351/326065

   Introduction Top

Protein-losing enteropathy is characterized by the loss of serum proteins into the gastrointestinal tract. It may lead to hypoproteinemia and clinically present as protein deficiency edema, ascites, pleural or pericardial effusion, and malnutrition. We report a challenging case of protein-losing enteropathy with thrombotic microangiopathic (TMA) features in a child.

   Case Report Top

A first-degree consanguineous and well-appearing 4-year-old boy was admitted to the pediatric ward for generalized edema evolving for 2 months. His medical history was marked in the neonatal period by the delayed passage of stool (beyond 24 h) in a full-term infant. In the 2nd week of life, he had a spontaneous resolution of acute intestinal occlusion. Because the child was lost to follow-up, he had no proper medical investigations. Since then, the boy had chronic constipation with a distended abdomen.

Meanwhile, he was under self-medication (lactulose and glycerol). At the examination, the child had stunting (weight = −3 standard deviation [SD], height = −4 SD, Gomez score = 56%, and Waterlow score = 63%), with various signs of malnutrition (skin pallor, brittle hair, scaling skin, significant fat, and muscle loss). Clinical signs of biologically verified zinc deficiency (xerosis, seborrheic-like dermatitis, and alopecia) were also identified.

Laboratory workup found features of losing protein enteropathy as follows: hypoalbuminemia = 11 g/l, hypocholesterolemia = 0.34 g/l, hypoferritinemia = 2 ng/ml. The boy had a euthyroid hormone profile (TSHus = 2.3 mU/l, T4 = 14 pmol/l, T3 = 4 pmol/l) and normal hepatic and renal functions. Total blood count however showed TMA features: normocytic normochromic anemia and thrombopenia (respectively, hemoglobin [Hb] = 3.5 g/dl, mean corpuscular volume = 98 fl, mean hemoglobin concentration = 30 pg, platelets = 42,000/mm3). White cell count, as well as lactate dehydrogenase (LDH) and haptoglobin levels, was normal. However, the reticulocyte count was low (<2%). Bone marrow aspiration was performed. Myelogram result was compatible with cobalamin or folic acid deficiency. Unfortunately, the child was recently transfused with blood, resulting in normal Vitamin B12 and folic acid tests (Vitamin B12 = 629 pg/ml, Vitamin B9 = 5.5 ng/ml). Oral nutritional rehabilitation was started. We started cobalamin and folic acid supplements due to cytopenia's recurrence, despite transfusion and adequate iron/zinc supplements. After what, we noticed a rapid continuous improvement in Hb and platelet count. The child also gained weight and generalized edema resolved by the 2nd week of hospitalization. As for the etiology of the enteropathy, medical history as well as medical examination (empty rectum with the explosive passage of stool afterward) was in favor of Hirschsprung's disease. Barium enema showed reduced caliber of the rectum, followed by a transition zone to an enlarged caliber sigmoid [Figure 1]. Radiograph's findings were typical of a short-segment Hirschsprung's disease. No ganglion cells, as well as increased acetyl cholinesterase staining at rectal suction biopsy, confirmed the diagnosis. Screening for other congenital disabilities associated with Hirschsprung's disease was negative. Surgery consisting of a primary pull-through procedure was performed.
Figure 1: Barium enema showing the reduced caliber of the rectum, followed by a transition zone to an enlarged caliber sigmoid

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The postoperative follow-up was unremarkable. Resection of the affected parts of the rectum led to a complete remission of the protein loss and complete recovery of the hematologic dysfunction by the 2nd month after surgery.

   Discussion Top

Protein-losing enteropathy is not a single disease; it is an atypical manifestation of other disease processes and is marked by excessive loss of protein into the gastrointestinal tract. These diseases can be classified into three broad groups according to the protein-loss mechanism: ulcerated lesions with protein exudation (e.g., peptic ulcer, inflammatory bowel disease, and gastric carcinoma), mucosal lesions without ulceration, but with increased permeability (e.g., Ménétrier's disease, celiac sprue, and eosinophilic gastroenteritis), and obstructive diseases (e.g., lymphoma), as well as a primary disorder of the lymphatic system (e.g., intestinal lymphangiectasia).[1] One of the several causes of protein-losing enteropathy is Hirschsprung's disease. Hirschsprung's disease occurs in one out of 5000 births.[2] The disease is caused by ganglion cells' failure to migrate cephalocaudally through the neural crest during 4–12 weeks of gestation,[3] causing an absence of ganglion cells in all or part of the colon. Varying lengths of the distal colon are unable to relax, causing functional colonic obstruction over time. The aganglionic segment usually begins at the anus and extends proximally.[4] The short-segment disease is most common and is confined to the rectosigmoid region of the colon.[5] Hirschsprung's disease is usually diagnosed in the neonatal period secondary to a distended abdomen, failure to pass meconium, and bilious emesis or aspirates with feeding intolerance.[6],[7] Failure to thrive with hypoproteinemia from protein-losing enteropathy is a less common presentation because Hirschsprung's disease is usually recognized early in the illness's course, but late forms have been known to occur.[8]

In our case, medical history was in favor of Hirschsprung's disease as the etiology of protein-losing enteropathy. However, the occurrence of TMA made diagnosis difficult. The myelogram was in favor of cobalamin deficiency; however, because the child was transfused with blood before tests, Vitamin B12 level was average. Cobalamin deficiency may result in hematologic characteristics similar to TMA (severe anemia and generally mild–moderate thrombocytopenia).[9] Reticulocytopenia is a universal finding that aids in differentiating cobalamin deficiency–TMA from other hemolysis.[9] Recovery after Vitamin B12 supplementation confirmed acquired cobalamin deficiency, presenting with TMA features in our case. With proper treatment, most patients with Hirschsprung's disease will not have long-term adverse effects and can have a healthy life.[10]

   Conclusion Top

Early diagnosis of Hirschsprung's disease is essential to avoid complications; however, it can lead to severe protein-losing enteropathy when misdiagnosed at birth. In our case, associated acquired cobalamin deficiency presenting with TMA features made diagnosis challenging. Medical treatment followed by surgery was efficient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


All authors express their thanks to all those who have helped in carrying out this work.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Lima MS, dos Santos Bomfim V, Zeinad A, Ctenas B, Arai MH. Association of protein-losing enteropathy caused by eosinophilic gastroenteritis with essential thrombocytosis: Case report. Clinics (Sao Paulo) 2006;61:271-4.  Back to cited text no. 1
Amiel J, Lyonnet S. Hirschsprung disease, associated syndromes, and genetics: A review. J Med Genet 2001;38:729-39.  Back to cited text no. 2
Parisi MA, Kapur RP. Genetics of Hirschsprung disease. Curr Opin Pediatr 2000;12:610-7.  Back to cited text no. 3
Feldmen M, Friedman LS, Sleisenger MH. Hirschsprung's disease: Congenital megacolon. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 7th ed. Philadelphia, PA: Saunders; 2002. p. 2131-5.  Back to cited text no. 4
Kessmann J. Hirschsprung's disease: diagnosis and management. Am Fam Physician 2006;74:1319-22.  Back to cited text no. 5
Loening-Baucke V, Kimura K. Failure to pass meconium: Diagnosing neonatal intestinal obstruction. Am Fam Physician 1999;60:2043-50.  Back to cited text no. 6
Khan AR, Vujanic GM, Huddart S. The constipated child: How likely is Hirschsprung's disease? Pediatr Surg Int 2003;19:439-42.  Back to cited text no. 7
Nelson Textbook of Pediatrics. 21st ed., Vol. 2. Available from: https://www.elsevier.com/books/nelson-textbook-of-pediatrics-2-volume-set/kliegman/978-0-323-52950-1. [Last accessed on 2020 Feb 02].  Back to cited text no. 8
Tran PN, Tran MH. Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: A systematic review. Transfus Apher Sci 2018;57:102-6.  Back to cited text no. 9
Coran AG, Teitelbaum DH. Recent advances in the management of Hirschsprung's disease. Am J Surg 2000;180:382-7.  Back to cited text no. 10


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