Prader-Willi syndrome complicates hereditary angioedema diagnosis

Key takeaways:

• A male patient presented to an outpatient clinic with abdominal swelling after a motor vehicle accident.
• The patient also presented with Prader-Willi syndrome, which can include hyperphagia and cognitive, psychiatric and gastrointestinal issues.
• The higher pain thresholds, difficulties in communication and diminished vomiting among patients with Prader-Willi syndrome may make diagnosis of hereditary angioedema difficult.

Prader-Willi syndrome can delay the diagnosis of hereditary angioedema, which already can be difficult to identify, according to a case report published in Annals of Allergy, Asthma & Immunology.

This may be the first case of a patient with both hereditary angioedema (HAE) and Prader-Willi syndrome (PWS), the authors of the case report wrote.

Initial misdiagnoses can delay the accurate and timely diagnosis of HAE, the authors wrote, noting previous research indicating a median 15-year delay between onset and correct diagnosis.

Incorrect diagnoses can lead to unnecessary treatment in addition to morbidity and mortality associated with pain, the authors continued, with syndromes such as PWS that dampen pain among the obstacles in the timely diagnosis of HAE.

“One of the reasons hereditary angioedema has a delayed diagnoses is due to its variable presentation and lack of specific symptoms,” Meaghan A. Callahan, BS, OMS-II, student at the Lake Erie College of Osteopathic Medicine-Elmira, told Healio.

“Patients with hereditary angioedema are typically unaware this disease exists unless there is family history due to its overall low incidence,” Callahan continued. “The painful symptoms are commonly misdiagnosed as irritable bowel syndrome, transient angioedema episodes or other abdominal disease processes.”

Caused by errors in genomic imprinting, PWS is rare and involves hyperphagia with life-threatening obesity, cognitive and psychiatric issues, and gastrointestinal issues including a high pain threshold and lack of vomiting. Patients with PWS might not experience typical responses to abdominal pain due to distention or swelling, the authors suggested.

In this case study, a man aged 61 years presented with PWS and abdominal swelling after a motor vehicle accident. The first presentation of this patient’s symptoms of HAE was unknown due to his concurrent diagnosis of PWS, although his family reported a history of the HAE type 1 phenotype.

In addition to this presentation, this patient had recently experienced arm swelling that had taken a week to resolve, along with swelling of his legs and abdomen following a previous car accident. 

Due to his PWS, the authors continued, the patient had high tolerance to pain that led to a continued shortage of symptoms as well as a lack of emesis that the abdominal distension could have caused, which in turn hindered early and affirmative diagnosis and treatment of HAE.

The patient had not experienced any clinical symptoms of HAE before the car accident that led to his visit with the outpatient clinic, the authors wrote, and some members of his family did not have the disease, so there were no suspicions that he might have had it as well.

The authors suggested that the patient may have experienced frequent abdominal episodes, but because of the syndromic lack of pain localization, his caregivers were unaware.

“The confounding effects of an increased pain tolerance and psychiatric issues make it difficult for these patients to express the symptoms they may be feeling,” Callahan said.

During a period when the patient was free of symptoms, testing indicated normal C4 (18 mg/dL) and C1q (16.3 mg/dL) levels and low C1 esterase inhibitor (20 mg/dL) and C1 esterase inhibitor function (50%) levels, which confirmed the HAE diagnosis.

“At the age of 61, the likelihood of angioedema attacks throughout the patient’s life is very possible, and something we will never know,” Callahan said.

Providers started the patient on subcutaneous icatibant as needed for rescue medication. Genetic testing revealed a heterozygous, pathogenic SERPING1 mutation that was contrary to family history but consistent with an HAE type 2 diagnosis.

This case illustrates how PWS can confound and mask the clinical characteristics that typically indicate HAE, the authors wrote, which can manifest as recurring and remitting abdominal pain caused by edema in intestinal tract walls, leading to nausea, vomiting and diarrhea.

The higher pain threshold among patients with PWS could decrease the externalization of the pain experienced during recurrent abdominal swelling attacks. The cognitive issues that these patients may experience can hinder communication about pain as well.

Additionally, patients with HAE may experience vomiting, but the decreased ability to produce emesis among patients with PWS may diminish this factor when providers are making a diagnosis.

When patients have a compounded diagnosis of PWS and HAE with mild symptoms, the authors recommended, providers should further explore the possibility of angioedema.

In this case, Callahan said, two major factors helped with the diagnosis of HAE.

“The first is the family history of this disease. There is possibility of a genetic component to this disease, which probed the idea of genetic testing in this patient,” she said. “The second factor was the patient’s presentation. When he came to the clinic, he presented with a second swelling attack, in a different part of his body, in the period of a month.”

The authors have not reported any follow-up of note with this patient.

“The major takeaway of this case for other physicians is to exhaust all diagnostic possibilities when it involves patients with increased pain tolerance and/or behavioral issues,” Callahan said.

“Patients suffering from diseases such as PWS may present with confounding issues different than the average patient,” she continued. “Thus, looking at the entire range of their symptom presentation is important in giving them a correct diagnosis to avoid unnecessary procedures or medications.”

For more information:

Meaghan A. Callahan, BS, OMS-II, can be reached at mcallahan68657@med.lecom.edu.