Blood stem cell transplant corrects defect underlying EPP in 16-year-old
In case of US teen, HSCT treatment helped avoid need for liver transplant
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A blood stem cell transplant successfully corrected the underlying defect that causes erythropoietic protoporphyria (EPP) and eased symptoms of the genetic condition in a 16-year-old boy in the U.S, according to a case report.
Prior to the stem cell transplant, the teen had developed painful sunlight sensitivity, a hallmark of EPP, and was experiencing severe abdominal pain, the researchers noted. The transplant was “used as a curative approach,” and led to “complete normalization of … clinical symptoms” in the patient, the team wrote.
Further, because the procedure — also known as HSCT, or hematopoietic stem cell transplantation — was performed before irreversible liver damage occurred, it also helped the teenager avoid the need for a liver transplant, the researchers noted.
“This case underscores HSCT as a disease-modifying therapy that may prevent the need for liver transplantation when performed before irreversible [liver] damage, ” the researchers wrote.
The study, “Hematopoietic stem cell transplantation for erythropoietic porphyria-induced acute liver failure: A case report and literature review,” was published in the journal Clinics and Research in Hepatology and Gastroenterology.
Porphyria refers to a group of genetic disorders in which the body’s ability to produce heme — a molecule that enables red blood cells to transport oxygen through the body — is disrupted. As a result, porphyrins and other heme precursor molecules, such as protoporphyrin, build up to toxic levels.
In EPP, which is caused by mutations in the FECH gene, excessive amounts of protoporphyrin accumulate mainly in red blood cell precursors in the bone marrow. Through the bloodstream, protoporphyrin can reach and build up in tissues such as the skin and liver.
Teen’s abdominal pain initially diagnosed as gastrointestinal infection
Although the main symptom of EPP is a painful skin sensitivity to sunlight, about 5% of people with the condition also develop progressive liver injury. This may eventually result in liver failure unless the patient undergoes a liver transplant. But because abnormal protoporphyrin production occurs in the bone marrow, the disease can recur even after a liver transplant.
For this reason, HSCT is often recommended for people with EPP who undergo a liver transplant. The procedure involves collecting blood cell precursors from a healthy donor, which are then infused into a patient’s bone marrow to correct the underlying defect that causes the disease.
HSCT may be performed before irreversible liver damage occurs, potentially preventing the need for a liver transplant, the researchers noted. However, such cases remain a few.
In this report, a team led by researchers at the University of California San Francisco described the case of a teen with EPP-related liver disease that was successfully treated with HSCT without a prior liver transplant.
The boy first came to the emergency department with severe abdominal pain along with nausea, vomiting, and diarrhea, which had lasted four days. Blood tests showed elevated liver enzymes and bilirubin levels, indicating liver injury.
Suspecting a gastrointestinal infection, doctors prescribed medications to relieve nausea and abdominal spasms, and the boy was discharged. Four days later, he returned with persistent abdominal pain and worsening vomiting. Blood tests showed further increases in liver enzyme levels and signs of declining liver function.
Extensive testing — for infectious, autoimmune conditions, and metabolic causes of liver disease — was negative, and imaging scans did not reveal any clear abnormalities. A liver biopsy eventually revealed signs of inflammation and unusual brown pigment deposits in the bile ducts, the channels that carry bile from the liver to the intestines.
Because his symptoms did not respond to standard treatment, doctors suspected an acute porphyria attack and started the boy on intravenous, or into-the-vein, hemin, marketed as Panhematin in the U.S. and Normosang in Europe. After several days of therapy, the boy’s abdominal pain and vomiting eased, and he was discharged.
No porphyria treatments, nor transplant, needed after HSCT
Further laboratory tests later ruled out acute porphyria but revealed markedly elevated levels of protoporphyrin in red blood cells. A reanalysis of the liver biopsy showed that the brown pigment deposits formed characteristic crystals, which suggested protoporphyrin buildup. Genetic analysis then identified two mutations in the FECH gene, confirming an EPP diagnosis.
Due to persistent episodes of abdominal pain and vomiting, along with rising liver enzyme levels, the boy was readmitted in the following weeks. He was restarted on hemin, along with other treatment approaches aimed at lowering his protoporphyrin levels and thereby protecting his liver.
Though evidence is limited, early HSCT may be the best preventive strategy to avoid liver transplant in severe cases like [that of] the reported patient.
Because the boy’s liver involvement had not yet progressed to irreversible damage requiring a transplant, the medical team and family decided to proceed with HSCT without first performing a liver transplant.
According to the team, the patient recovered well and was discharged from the hospital 27 days later. At that time, he no longer needed porphyria treatments, and lab tests showed a marked drop in protoporphyrin levels, which approached normal values within three months. Liver enzyme and bilirubin levels also stabilized and remained within the normal range, indicating improved liver function.
“Though evidence is limited, early HSCT may be the best preventive strategy to avoid liver transplant in severe cases like [that of] the reported patient,” the researchers wrote. “Further studies are required to define optimal patient selection criteria and timing for HSCT in protoporphyria [liver disease] management.”
