"True" Linitis Plastica

Submitted by Rahim Dhanani, Louise Man and Sami Tahhan

Published October 6, 2019

A 28-year-old wheelchair bound white male with Angelman syndrome, cerebral palsy and seizure disorder was hospitalized for breakthrough seizures. During outpatient hospital follow up, review of laboratory data from the hospitalization revealed an anemia with hemoglobin of 9 mg/dL (baseline 13 mg/dL) and normal red cell distribution width (RDW). History per caretakers was negative for recent traveling, changes in medications, trauma, low-iron diet, fevers, night sweats, weight loss, cough, diarrhea, vomiting, hemoptysis, hematemesis, hematochezia, melena or hematuria. There was no prior history of autoimmune disease, renal disease, or gastrointestinal surgeries. No family history of anemia or hemoglobinopathies was present. Physical examination and vital signs were unremarkable, including no jaundice, petechiae, ecchymosis or bruising. Iron studies were indicative of iron deficiency anemia. Peripheral blood smear was normal without target cells or basophilic stippling. All other laboratory results were normal including normal white blood cell, platelet and reticulocyte counts; normal urinalysis without RBCs or occult blood; and negative fecal occult blood testing. Upper endoscopic evaluation via esophagogastroduodenoscopy (EGD) revealed a plastic-like foreign body in the stomach measuring roughly 2 cm in width (Figure 1). Multiple attempts to endoscopically remove the foreign body were unsuccessful. 

Questions:

• 1. What is the next best step in the management of this patient?

A: Repeat EGD for foreign body removal 

B: Gastrotomy for foreign body removal 

C: Partial gastrectomy 

D: Observation and iron supplementation 

• 2. Which of the following is associated with Angelman syndrome?

A: Hyperphagia (Excessive eating)

B: Obesity & Type II Diabetes

C: Fascination with crinkly objects

D: Hypermimia (Excessive speaking)

3. Which set of iron study results are indicative of iron deficiency anemia? 

4. What is the most common cause of Angelman’s syndrome?

A: Paternal uniparental disomy

B: Maternal uniparental disomy

C: 15q11-13 maternal deletion

D: 15q11-13 paternal deletion 

Answers:

Question 1: Answer: D. Observation and iron supplementation

The management of foreign body ingestions are dependent upon the type of object and its location within the gastrointestinal tract. In general, asymptomatic patients with blunt, non-erosive foreign bodies that have passed into the stomach are managed conservatively as most will pass spontaneously within 1-4 weeks1. Exceptions to this rule include disk batteries, magnets, objects longer than 6 cm and/or wider than 2.5 cm and objects that fail to pass beyond the stomach after 3-4 weeks1. Patients who are managed conservatively should be monitored to confirm passage of the object. Surgical intervention is reserved for complications such as perforation, bleeding or obstruction. 

Our patient was stable, asymptomatic and had a blunt, malleable object less than 2.5 cm in width located in the stomach, making his case amenable to conservative management with close monitoring. Given resolution of anemia with iron supplementation, we hypothesize that the foreign body acted as a mechanical barrier to absorption that could be overcome by increasing iron intake. Unfortunately, our patient eventually developed hematemesis, requiring urgent foreign body removal. Fortunately, our patient did not require surgical intervention as more aggressive endoscopic retrieval attempts were successful and revealed the foreign body to be a plastic glove (Figure 2).

Question 2: Answer: C. Fascination with crinkly objects.

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are two well-documented genetic neurodevelopmental disorders due to abnormalities on chromosome 15. Despite this similarity, they have very distinct clinical courses. PWS is characterized by mild to moderate intellectual disability and hyperphagia (A) leading to obesity and type 2 diabetes3 (B). AS, on the other hand, is characterized by severe intellectual disability; ataxic limb movements; absence of speech (D); and epilepsy, accompanied by a happy sociable disposition and unprovoked bouts of laughter2. 

Interestingly, patients with AS also commonly exhibit behaviors including excessive mouthing as well as a fascination with water and crinkly objects such as paper and plastic2 (C). These characteristic behaviors clearly played a role in our patient’s ingestion of a plastic glove. Furthermore, it is important to note that although foreign body ingestions are most commonly found in the pediatric population, specific adult populations also at risk include those with developmental delay, psychiatric conditions, substance intoxication and persons seeking secondary gain.

Question 3: Answer: C.

Iron deficiency anemia, anemia of chronic disease, thalassemia and sideroblastic anemia commonly present as microcytic anemias (MCV < 80 fL). Microcytic anemias are commonly investigated via iron studies, which include serum ferritin (marker of iron stores in macrophages), serum iron, transferrin iron binding capacity (TIBC; direct measure of serum transferrin) & transferrin saturation (Iron/TIBC).

Iron deficiency anemia occurs due to low serum iron levels and is either caused by decreased absorption (e.g. Celiac disease), insufficient dietary intake (e.g. malnutrition), increased utilization (e.g. pregnancy) or blood loss (e.g. colorectal cancer). Low total body iron (↓ Iron) results in low iron stores (↓ Ferritin). Liver detects low iron stores and upregulates transferrin production (↑ TIBC), which leads to a low transferrin saturation (↓ Iron/↑ TIBC). 

Question 4: Answer: C. 15q11-13 maternal deletion

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are two well-documented genetic disorders attributed to genomic imprinting, meaning that gene expression is dependent upon the gender of the parent donating the gene. AS is caused by the lack of a maternal copy of the UBE3A gene located on chromosome 15q11-13, thus the patient will have two paternal copies2. Most cases of AS (about 70%) are caused by a deletion of the maternal copy of the gene2 (C). About 10% are due to a mutation in the UBE3A gene, 5% are caused by abnormalities in the imprinting center of chromosome 15 and only 2% are caused by paternal uniparental disomy2 (A). Uniparental disomy occurs when an error during meiosis leads to an offspring receiving two copies of a chromosome from only one of the parents. Most cases of PWS (about 70%) are caused by paternal deletion of the critical region on chromosome 15q11-13 (D) and about 25% are due to maternal uniparental disomy3 (B).

References:

1. Birk M, Bauerfeind P, Deprez P, et al. Removal of foreign bodies in the upper gastrointestinal tract in adults: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2016; 48:489–96. 

2. Clayton-Smith J. Angelman syndrome: a review of the clinical and genetic aspects. Journal of Medical Genetics. 2003; 40:87–95. 

3. Angulo MA, Butler MG, Cataletto ME. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. Journal of Endocrinological Investigation. 2015;38:1249-1263. 

Brief Bios:

Rahim M. Dhanani, MS is a 4th year medical student at Eastern Virginia Medical School in Norfolk, Virginia. 

Louise Man, MD is a hematology and oncology professor and attending physician at the University of Virginia in Charlottesville, Virginia. 

Sami Tahhan, MD is an internal medicine professor and attending physician at Eastern Virginia Medical School in Norfolk, Virginia.