Porphyria Testing Urged in Study for Certain Cyclic Vomiting Patients

Researchers pinpoint clinical features to prompt genetic testing in CVS

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by Steve Bryson, PhD |

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For people with cyclic vomiting syndrome (CVS) — a condition whose symptoms significantly overlap those of porphyria — a long disease duration, taking very hot showers/baths to alleviate symptoms, and having co-existing conditions, all are clinical features to prompt genetic testing for acute porphyria, according to a new study.

CVS is characterized by episodes of abdominal pain, nausea, and vomiting, which are similar to symptoms associated with acute porphyria attacks.

Researchers had sought to pinpoint the clinical features of CVS that could suggest whether patients with the vomiting disorder also could have acute porphyria and should undergo genetic testing.

Although none of the cyclic vomiting syndrome patients in this study tested positive for mutations in genes related to porphyria, researchers recommended a spot urine test for porphyria-related markers during an acute CVS episode to identify those who might have acute porphyria.

Researchers also noted that larger studies are needed to determine the prevalence of acute porphyria in the CVS population.

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Disorders with overlapping symptoms

Titled “Prevalence of Undiagnosed Acute Hepatic Porphyria in Cyclic Vomiting Syndrome and Overlap in Clinical Symptoms,” the study was published in the journal Digestive Diseases and Sciences.

Porphyrias are a group of genetic conditions caused by disruptions in the production of heme, a molecule essential for transporting oxygen in living cells. Such disruptions lead to the toxic buildup of heme precursors in various tissues. In cutaneous porphyrias, symptoms primarily affect the skin, whereas in acute porphyrias they mainly affect the nervous system.

Acute porphyrias are marked by sudden attacks of severe abdominal pain, nausea, and vomiting. Other accompanying symptoms may include anxiety, confusion, insomnia, muscle pain and weakness, and a burning or prickling sensation. Red-to-brownish urine can occur, as well as skin lesions on sun-exposed areas, in certain types of acute porphyrias.

CVS is a gut-brain interaction disorder characterized by repeated episodes of nausea and vomiting without an apparent cause.

Similarly to acute porphyria, these episodes alternate with longer periods of no symptoms. As such, there is a considerable overlap in symptoms between acute porphyria and CVS.

However, it is unclear whether there is a subset of CVS patients who have underlying porphyria.

To find out, investigators in the U.S. invited adults with CVS to complete a detailed questionnaire regarding their symptoms.

To be eligible for porphyria genetic testing, patients had to have experienced recurrent episodes of severe abdominal pain alongside two or more other symptoms. These typical porphyria symptoms included red/brownish urine, blistering skin lesions, muscle weakness, numbness, tingling, mental health impairment, high blood pressure (hypertension), irregular heartbeat, or constipation.

The survey was completed by 234 individuals, with a mean age of 38.7. Among them, 180 (76.9%) were female. Most participants reported anxiety (68.4%), depression (55.6%), and a history of migraines (53.4%). Irritable bowel syndrome (26.9%), chronic fatigue syndrome (16.2%), and fibromyalgia (10.3%) also were noted as symptoms.

Nearly two-thirds (63.7%) of patients said CVS interfered with their job, and about half (47.4%) took very hot showers or baths to alleviate CVS symptoms.

Although two individuals reported a family history of porphyria, neither had markers for the disease in their urine, analyzed prior to study participation. Samples were tested for the heme precursors porphobilinogen (PBG) and aminolevulinic acid (ALA).

During a CVS episode, more than 85% of participants experienced various nervous system symptoms, similar to those of acute porphyrias. Reddish-brown urine was reported in 60.3% of cases. About a quarter (23.5%) of the patients reported blistering skin lesions during a CVS episode.

“The reasons for this finding are unclear, and future research to objectively assess these findings are warranted,” the team wrote.

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Genetic testing nets no positive results

Tests to identify genetic mutations associated with known porphyria types were completed by 91 of the eligible CVS patients. Among them, only two carried variants of uncertain significance (VUS), which are previously identified genetic variants whose impact in porphyria is unknown.

These variants were found in the HMBS gene, which is associated with a form of porphyria called acute intermittent porphyria. Urinary tests for ALA and PBG, completed by one of these two individuals, were normal. The remaining 89 participants tested negative for mutations that cause, or likely cause, acute porphyria.

Individual clinical factors that predicted the need for porphyria genetic testing in CVS patients included inpatient hospitalization due to CVS symptoms in the past year and the presence of co-existing medical conditions.

Eligible participants also were more likely to have irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, depression, and migraines.

Researchers also noted that the eligible patients were more like to take hot baths/showers to ease their symptoms, and to have job problems because of CVS.

In the final adjusted statistical calculations, co-existing conditions, longer duration of CVS symptoms, and hot showers/baths were identified as predictors for acute porphyria testing eligibility in CVS patients.

Conversely, gender, age, ethnicity, cigarette use, and cannabis use were not predictive.

“Our study did not reveal any individuals who were positive for [acute porphyria] based on genetic testing,” the researchers wrote. “Although the prevalence of [acute porphyria] is small in the general population, we had hypothesized that an enriched sample with symptoms of [acute porphyria] might yield positive results.”

Nonetheless, further testing should be done in this patient population, the team recommended.

“Prompt and accurate diagnosis and treatment of both CVS and AHP will greatly improve patient outcomes and reduce unnecessary investigations and healthcare utilization,” they wrote.