New ABCB4 mutation found to be cause of PFIC3 in young woman
Researchers: Differences in variants may affect treatment response
A new mutation in the ABCB4 gene was found to cause progressive familial intrahepatic cholestasis (PFIC) type 3 in a young woman, a case study shows.
The woman responded well to treatment with ursodeoxycholic acid (UDCA), which isn’t always effective in people with this type of PFIC. The study’s researchers suggested that differences between disease-causing ABCB4 mutations may influence how the disease responds to cholestasis treatment.
“Identifying ABCB4 mutations can guide treatment, as shown by our patient’s response to UDCA, avoiding liver transplantation,” the researchers wrote. The case report, “Novel ABCB4 mutation in a female patient with progressive familial intrahepatic cholestasis type 3: a case report and literature review,” was published in the Annals of Medicine and Surgery.
PFIC comprises a group of genetic disorders that are marked by intrahepatic cholestasis, where the flow of the digestive fluid bile from the liver to the intestines is impaired. Left untreated, cholestasis can lead to liver damage and liver failure, leaving a transplant the only therapeutic option.
Common symptoms include jaundice, or the yellowing of the skin and whites of the eyes, dark urine, and itchy skin.
There are several different types of PFIC, each linked to mutations in different genes. PFIC type 3 (PFIC3) is caused by mutations in both copies of the ABCB4 gene and typically results in symptoms later in childhood or adulthood.
Many different ABCB4 mutations can cause PFIC3 and new ones are still being identified. Within the last year alone, several new PFIC3-causing mutations have been reported. The specific mutation may influence how the disease manifests and how it responds to treatment.
A new mutation
Here, researchers reported the case of a young woman who carried a new ABCB4 mutation that was the likely cause of her PFIC3.
The woman first sought medical attention at age 16 due to abdominal pain that was accompanied by increases in markers of liver damage. At the time, she didn’t show any signs of overt liver dysfunction, so doctors didn’t test further and focused on managing her symptoms.
Her parents, who were blood related, were healthy, but her maternal grandmother had a history of bile duct stones and her paternal uncle had died at age 30 due to liver cirrhosis (irreversible liver scarring). Bile duct stones are hardened bile deposits that become trapped in the tubes that transport bile, which can cause cholestasis.
Two years later, the woman was admitted to the hospital again with abdominal pain, fever, and jaundice.
Further diagnostic tests at this time showed signs of potential cholestasis, including dilated bile ducts, a stone in a bile duct, and chronic inflammation of the gallbladder, which stores bile between the liver and the intestines. The woman also had other signs of liver damage, including an enlarged liver and spleen, high levels of liver damage markers, and scarring on a biopsy.
Based on these findings and her family history, clinicians ordered genetic testing. This revealed a mutation, dubbed c.2870G>T, in both copies of the ABCB4 gene, a previously unreported mutation, but computer modeling indicated it would likely be disease-causing. Based on this result, the woman was diagnosed with PFIC3.
After the diagnosis, she was started on UDCA (sold as Urso and Actigall), a standard cholestasis treatment that helps promote bile flow. Her symptoms resolved, her liver function normalized within a few months, and she hasn’t shown any signs of liver damage during follow-up visits.
The researchers then reviewed data from 108 PFIC3 cases in the literature that were caused by different ABCB4 mutations. They found variable responses to UDCA, with fewer than half the cases responding to it.
“Variability in PFIC3 presentation and treatment outcomes, as demonstrated by our review of 108 cases, highlights the need for personalized approaches,” the researchers wrote. “While PFIC3 patients with other ABCB4 mutations have varied responses to UDCA, this specific mutation resulted in a complete biochemical remission without the need for liver transplantation.”
They said the woman’s case “adds to the growing body of evidence that [mutation-specific] approaches may enhance patient care and optimize treatment strategies for this rare disease.”
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