Porphyria Research Finds Gene Linked to Severity of Skin, Liver, Nervous System Symptoms

Woman scratching her arm
Woman scratching her arm

One of the mysteries that has surrounded porphyria is why some people, despite having the same genetic defect, can have such differing degrees of symptoms. Porphyria activity can affect the skin, liver, or nervous system depending on type and cases can range from mild to requiring intensive hospitalization. A team of researchers, working with St. Judge Children’s Research Hospital, believe they have found a gene that could be connected to the severity of the disease.

In Brief: Porphyria

Porphyria comes in different types depending on which parts of the body are affected, but they all share a root cause: heme production. Heme is a component of hemoglobin, the protein that lets red blood cells carry oxygen. The body produces heme using a number of different enzymes. If a genetic variation causes a shortage of one of these enzymes, the process can go awry and cause a buildup of various other chemicals used in heme production that lead to symptoms. Porphyria is sometimes known as the “vampire disease” because, if the condition affects the skin, symptoms such as blisters, swelling, and pain can be triggered by sunlight.

The New Gene Variation

The researchers ended up focusing on the ABCB6 gene, also known as “Lan”. Variations in this gene were associated with increased toxic build-up of the symptom-inducing chemicals. Further investigating found that the Lan variant was also more common in patients with severe porphyria activity than in those with milder symptoms.

Among the 36 porphyria patients included in the study, those with rare ABCB6 variants were more likely to require admittance to intensive care units at a rate of 62%, versus 7% for other porphyria patients.

By using mouse models, the researchers found that the ABCB6 variants were incapable of transporting porphyrins, a type of pigment category that heme belongs to. This finding implies that porphyrin transport proteins may play a role in porphyria—the first known report to do so.

Understanding more about the possible connections between porphyrins, gene ABCB6, and porphyria, is required before any potential porphyria treatments can be devised or tested. For now, the researchers are looking at medications known to cause drug-induced porphyria to see if they can interfere with porphyrin transportation. Although drug-induced porphyria usually affects just the skin, findings in this area may have other implications for the liver and nervous system variants.

“Rare genetic variations may solve mystery of porphyria severity in some patients,” St. Jude Children’s Research Hospital web site, August 10, 2016; https://www.stjude.org/media-resources/news-releases/2016-medicine-science-news/rare-genetic-variations-may-solve-mystery-of-porphyria-severity-in-some-patients.html, last accessed August 10, 2016.