PRADER WILLI SYNDROME AND PHYTOBEZOAR

by Monzur Ahmed

One of my favourite TV shows is the forensic crime drama “CSI: Crime Scene Investigation" (the original Las Vegas version, starring William Peterson as Gil Grissom, not the subsequent spin-offs). The show ran for 15 seasons. In one memorable episode entitled “Dog Eat Dog,” the body of a man is found in a dumpster; cause of death unknown [1]. What appears to be blood on his lips turns out to be cranberry sauce. Initially foul play is suspected but it transpires that the man died from asphyxia caused by gastric distention. The postmortem revealed vast amounts (and variety) of food in the stomach. After some detective work, Grissom diagnoses Prader-Willi syndrome, a condition associated with an insatiable appetite. The dead man literally ate himself to death having won a food-eating contest along the way! When I first watched this episode of CSI, I marvelled at the ingenuity of the script writers. A few days ago, I was reminded of “Dog Eat Dog" by a patient...

​A 22 year old man was admitted to my hospital with a one day history of severe abdominal pain, distention and nausea but no vomiting. He was still opening his bowels and passing wind. He had a history Prader-Willi syndrome and had spinal surgery for scoliosis at age 10 years. There was also a history of anxiety. For 3 years he had been living in a Residential Home where his meals were regulated. He was a vegetarian. On examination, he was not obese (BMI 20 kg/m^2) and had a distended, tender abdomen. Initial AXR showed a very distended stomach containing food material. A CT scan confirmed these findings and worryingly the report mentioned “imminent danger of perforation.” The surgeons were called in, presumably with a view to surgery, but instead they asked me to do an OGD to see if there was anything that could be done endoscopically. A large phytobezoar was found in the stomach which proved challenging to treat (see video)... ​

Prader-Willi syndrome (PWS) was first described by Prader et al. in 1956 and is now recognised as a multisystemic complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region [2,3]. There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion (65–75 % of cases), maternal uniparental disomy 15 (20–30 % of cases), and imprinting defect (1–3 %). Clinical manifestations change with age with hypotonia and a poor suck resulting in failure to thrive during infancy. As the individual ages, other features such as short stature, food seeking/ hyperphagia with excessive weight gain, developmental delay, cognitive disability and behavioural problems become evident. The phenotype is likely due to hypothalamic dysfunction, which is responsible for hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency. Obesity and its complications are the major causes of morbidity and mortality in PWS. Hyperphagia (constant eating due to an insatiable appetite) is a common feature in individuals with PWS. In one study, four reports of unexpected mortality due to gastric rupture and necrosis were found in 152 reported deaths in individuals with PWS, accounting for 3% of mortality [4]. Four additional individuals were suspected to have gastric rupture. Vomiting and abdominal pain, although rare in PWS, were frequent findings in this cohort. A bezoar is an indigestible conglomeration trapped in the gastrointestinal tract. This indigestible mass can be formed by a variety of materials that were intentionally or accidentally ingested [5]. Bezoars are mainly classified into four types depending on the material constituting the indigestible mass of the bezoar: phytobezoars, trichobezoars, pharmacobezoars, and lactobezoars. Gastric bezoars can cause outlet obstruction, ulcerative lesions and subsequent bleeding, whereas small intestinal bezoars present with small bowel obstruction and ileus. The currently available treatment options for a gastric phytobezoar include dissolution of the bezoar by Coca-Cola®, removal by endoscopic devices, laparotomy, and laparoscopic surgery. To my knowledge, phytobezoar as a result of hyperphagia has not been previously reported as a complication of PWS.

REFERENCES
1. CSI: Crime Scene Investigation, season 6, episode 9, "Dog Eat Dog"
https://www.csifiles.com/reviews/csi/dog_eat_dog.shtml
2. Prader A, Labhart A, Willi H. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach myatonieartigem Zustand im neugeborenenalter. Schweiz Med Wochenschr. 1956;86:1260–1261.
3. Angulo MA, Butler MG, and Cataletto ME, J Endocrinol Invest. 2015; 38: 1249–1263. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630255/
4. Stevenson DA et al J Pediatr Gastroenterol Nutr. 2007 Aug; 45(2): 272–274., Gastric Rupture and Necrosis in Prader-Willi Syndrome
https://www.ncbi.nlm.nih.gov/pubmed/17667731
5. Iwamuro M et al, World J Gastrointest Endosc. 2015 Apr 16; 7(4): 336–345.Review of the diagnosis and management of gastrointestinal bezoars
​https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400622/