Pediatric porphyria cutanea tarda often goes undiagnosed: Study
Genetic predisposition found to play central role in childhood onset of disease
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Diagnosis of porphyria cutanea tarda (PCT), the most common form of porphyria, is rare during childhood, and it can be easily overlooked when symptoms first appear early in life, a study in Argentina reveals.
Despite showing hallmark PCT symptoms, nearly one-third of affected children were not diagnosed until adulthood, sometimes decades after their first signs appeared. The study also found that genetic predisposition plays a central role in childhood-onset PCT. In addition, environmental exposures, such as sunlight, agricultural chemicals, and certain medications, may exacerbate symptoms or trigger an earlier onset of the disease.
“This study provides considerable insight into the genetic and environmental origins of pediatric onset of PCT in an Argentinian population,” researchers wrote, emphasizing the need for early recognition, genetic evaluation, and avoidance of known precipitating factors.
The study, “Porphyria cutanea tarda in children: epidemiological study of a rare disease in Argentina,” was published in Medicina (Buenos Aires).
‘Few cases of PCT with onset in childhood have been reported to date’
PCT, similar to other types of porphyria, occurs when the body cannot properly produce heme, an iron-containing molecule essential for transporting oxygen throughout the body. In PCT, this can occur when mutations in the UROD gene lead to a deficiency of uroporphyrinogen decarboxylase (UROD), one of the key enzymes necessary for heme production. However, in most cases, PCT is acquired rather than inherited and is triggered by various factors, including alcohol abuse, certain diseases, or medications.
When UROD activity is low, heme precursors called porphyrins accumulate mainly in the liver and circulate to the skin, making it abnormally sensitive to sunlight and triggering blisters or other skin lesions after even brief sun exposure.
“Few cases of PCT with onset in childhood have been reported to date,” the researchers wrote, noting they aimed to provide a comprehensive analysis of these rare presentations.
For this study, the team reviewed data from 28 children and adolescents who received a diagnosis of PCT at the Center of Investigations on Porphyrins and Porphyrias (CIPYP) at the University of Buenos Aires in Argentina between 1977 and 2025.
The group included 15 boys and 13 girls. Symptoms first appeared between the ages of 3 and 16, with a median age at diagnosis of 11. Although most children were diagnosed at or shortly after symptom onset, eight (28.6%) were only diagnosed in adulthood, between the ages of 32 and 63, highlighting limited clinical awareness of pediatric PCT.
While 20 children (71.4%) had no known affected family member, four had relatives who also developed early-onset PCT, indicating a hereditary component.
All children showed hallmark skin symptoms of the disease, including fragile skin, blistering on sun-exposed areas, changes in skin color or thickness, and excessive hair growth. Lab testing revealed elevated porphyrin levels in urine and blood, and enzyme studies confirmed reduced UROD activity.
Analysis reveals wide range of mutations in UROD gene
Genetic analysis, performed in 24 of the 28 patients, revealed a wide range of mutations in the UROD gene. The most common was c.11dupA, found in seven (35%) non-related patients, which is consistent with its observed frequency in Argentina. Several other previously reported variants were also detected, indicating that many of the same genetic changes observed in adults can also occur in childhood-onset cases, the researchers noted.
A newly identified mutation, a small deletion called c.752delC, further broadened the genetic diversity seen in the group.
Several potential triggers for disease onset were also identified, including iron or vitamin supplementation, hepatitis virus infections, and hemodialysis — a treatment that filters the blood when the kidneys are unable to function properly. In many children, more than one triggering factor was present.
The researchers also noted that most children lived in rural areas, where prolonged sun exposure from outdoor and agricultural work, combined with possible exposure to environmental toxins such as pesticides and herbicides, may have worsened symptoms and contributed to earlier disease onset in those genetically predisposed.
This study provides a comprehensive analysis of childhood-onset PCT in the Argentinian population, shedding light on both genetic and environmental factors contributing to the disease.
A similar effect may have been triggered by certain medications known to alter liver function and taken by some children.
Even so, the authors emphasized that hereditary factors play the primary role in pediatric PCT, with environmental factors acting as secondary contributors. Thus, they stressed the importance of genetic evaluation in children and their families to facilitate early diagnosis and effective management.
Treatment with S-adenosyl-L-methionine (SAM), a compound that supports liver function, together with low-dose chloroquine to help clear excess porphyrins — or SAM alone for those on hemodialysis — led to clear improvement in all children. Most recovered within about 60 days, or about two months, the researchers reported.
“This study provides a comprehensive analysis of childhood-onset PCT in the Argentinian population, shedding light on both genetic and environmental factors contributing to the disease,” the researchers concluded. “We emphasize the crucial need for early diagnosis, particularly in pediatric cases, and remark on the importance of genetic studies among family members to prevent the delayed recognition of PCT in high-risk individuals.”
