For young girl with fragile skin, sun protection proves crucial to care
Meds ineffective for 2-year-old with HEP, but shielding from sunlight helps
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For a young girl newly diagnosed with a type of porphyria that makes skin extremely sensitive to light, strict sun protection — including simple measures such as wearing wide-brimmed hats outdoors — was found to ease blistering lesions on her skin, as detailed in a case study.
The researchers noted that medications such as cholestyramine and cimetidine showed little to modest benefit for the 2-year-old from Brazil, who was found to have hepatoerythropoietic porphyria (HEP) when evaluated at a U.S. hospital. Earlier genetic testing in Brazil had shown the child had two gene mutations, one inherited and one newly present.
Measures to prevent sunlight exposure, including wearing protective clothing and limiting time outdoors, were started after that initial testing, and ramped up after the child’s HEP diagnosis. They helped reduce many of the girl’s symptoms, the researchers noted.
“Rigorous light protection was linked to marked improvement,” the team wrote.
According to the researchers, “this case adds to the limited published literature on treatment response in HEP by allowing descriptive comparison across several distinct therapeutic phases.”
The authors described the girl’s case in a study titled “Hepatoerythropoietic porphyria in a 2-year-old child: Clinical features and effects of treatment,” which was published in the journal Molecular Genetics and Metabolism.
Porphyria occurs when the body cannot produce heme, a part of the protein that carries oxygen in red blood cells. As a result, porphyrins, which are precursors to heme, build up and cause symptoms that typically affect either the skin or the nervous system.
In HEP, usually marked by fragile skin, the condition is due to mutations in both copies of the UROD gene. UROD provides instructions for an enzyme of the same name that’s needed to produce heme.
Genetic testing showed 2 mutations in UROD gene
The child treated in this case developed symptoms of HEP during her first year of life. She required intensive care shortly after birth, and abdominal imaging showed an enlarged spleen and liver. When she was about 10 months of age, her parents noticed recurrent blisters and open sores on her face and arms.
Her skin was unusually fragile, and the sores healed very slowly, sometimes taking months. While the lesions were itchy, they generally were not painful unless she scratched them.
The girl also developed dark urine and mild gray discoloration of her teeth, the team noted. Doctors considered allergies to food or environmental substances, but tests came back negative.
Before she was evaluated, at 2.5 years of age, at the Massachusetts General Hospital Porphyria Center in the U.S., genetic testing in Brazil had identified two mutations, or variants, in the UROD gene: c.239C>G and c.464C>T. Testing of her parents showed that she inherited the first variant from her father, while the second variant developed anew.
Additional testing at Massachusetts General confirmed a diagnosis of HEP. UROD activity in the child’s red blood cells was only about 5% of normal. Porphyrins were greatly increased in her blood, urine, and stool, the tests showed.
She also had evidence of mild hemolysis, which means that red blood cells were being destroyed somewhat faster than usual. Her hemoglobin, the protein that carries oxygen in red blood cells, was normal or only mildly low. Haptoglobin, which binds to free hemoglobin when red blood cells are destroyed, was low, while lactate dehydrogenase, released from destroyed red blood cells, was elevated.
The girl’s blood had elliptocytes, which are oval-shaped red blood cells; target red blood cells, which have a target-like appearance; and dacrocytes, which are red blood cells shaped like a teardrop. Her enlarged spleen and liver were consistent with hemolysis. However, her liver had normal stiffness and no fatty liver disease.
New treatments are needed for this rare disorder, researchers say
Because excess porphyrins make the skin extremely sensitive to light, the most important treatment was strict protection from sunlight, the researchers noted.
“Rigorous light-protection measures, including long sleeves, long pants, gloves, wide-brimmed hats when outdoors, and minimizing time outdoors, began after identification of the UROD variants,” the team wrote.
Sunscreen was also recommended. After these measures were introduced, the frequency and severity of her blistering lesions decreased, the team noted. However, her parents did note that the gray discoloration of her teeth became slightly more noticeable over time.
Rigorous light-protection measures [included wearing] long sleeves, long pants, gloves, wide-brimmed hats when outdoors, and minimizing time outdoors, .
Doctors also prescribed cholestyramine, which may help by binding porphyrins in the intestine and increasing their removal, but it showed no clear benefit. Cimetidine, normally used to reduce stomach acid, was linked to lower levels of porphyrins in her urine, although the benefit was modest.
The girl also underwent therapeutic phlebotomy, which involves removing a controlled amount of blood to reduce levels of red blood cells or iron. About 10 mL of blood per kilogram of body weight was removed every 3 to 4 weeks, for six treatments, while cimetidine was continued.
Porphyrins did not show a consistent decrease, however, which led the team to conclude that phlebotomy did not provide clear benefit in this case.
According to the team, “this case highlights the importance of considering HEP in children with blistering lesions on sun-exposed skin.”
The researchers noted that “management included strict photoprotection and sequential trials of cholestyramine and cimetidine, followed by serial therapeutic phlebotomy while continuing cimetidine. Neither cholestyramine nor therapeutic phlebotomy was associated with clear biochemical improvement, whereas cimetidine was temporally associated with a decline in urinary porphyrins.”
Noting that “effective therapies for HEP have not been identified,” the researchers concluded that “additional study of treatment approaches for this rare disorder is needed.”
This little girl’s case “highlights the diagnostic value of combining genetic and functional data and illustrates the challenges of assessing treatment response over time in a rare porphyria,” the team wrote.
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