Testing umbilical cord blood can help ID porphyria in newborns
Blood collected at birth used to screen for EPP, XLP in small study
Testing umbilical cord blood can help identify newborns with undiagnosed erythropoietic protoporphyria (EPP) or X-linked protoporphyria (XLP), two inherited forms of porphyria marked by extreme sensitivity to light, according to a small study from the U.K.
While symptoms of these diseases generally emerge at 1 year of age, extremely young patients may be at risk of painful light sensitivity while undergoing phototherapy for jaundice, a condition that commonly arises in newborns.
Jaundice is marked by a yellowing of the skin, white parts of the eyes, and mucus membranes due to the accumulation of a yellow pigment in the body called bilirubin. The recommended treatment is phototherapy, a technique that uses light to help break down excess bilirubin.
According to the researchers, patients with these porphyrias are particularly sensitive to certain wavelengths, potentially even as newborns, and may require special precautions.
“We propose analysis of cord blood porphyrins [precursor molecules] to identify infants at risk of acute painful photosensitivity … should phototherapy for neonatal jaundice be required in the first few weeks of life,” the researchers wrote. Such testing could be done for infants with siblings or both parents who have the condition, the team noted.
Their study, “Cord blood porphyrin analysis in neonates at risk of inheriting protoporphyria: An observational cohort study,” was published in the British Journal of Haematology.
Porphyria is a group of conditions in which mutations in certain genes disrupt the production of heme, a molecule used by red blood cells to transport oxygen throughout the body. As a result, heme precursors, called porphyrins, build up to toxic levels in different tissues and organs.
EPP, XLP both marked by skin hypersensitivity to light
EPP and XLP are two inherited types of porphyria, with EPP caused by mutations in the FECH gene and XLP resulting from mutations in ALAS2. Both lead to elevated levels of protoporphyrin IX, and are characterized by skin hypersensitivity to sunlight and some types of artificial light, like fluorescent lights.
Jaundice is a common condition that occurs in newborns and is typically unrelated to EPP and XLP, though it can also occur in these patients. As a first-line treatment for newborn jaundice, the American Academy of Pediatrics recommends phototherapy, a method that uses special blue-green light to help break down excess bilirubin.
Now, a research team from institutions across the U.K. investigated whether blood collected from the umbilical cord at birth can be used to screen for EPP and XLP. Such screening could potentially prevent skin hypersensitivity with jaundice-related phototherapy for infants who may have these conditions, the team noted.
“Given the potential for visible light to precipitate painful skin reactions in babies with protoporphyria, planned urgent cord blood porphyrin testing at birth of neonates at risk of inheriting protoporphyria may indicate whether special precautions need to be taken, should phototherapy be required,” the researchers wrote.
Researchers established parameters for testing umbilical cord blood
From 20 cord blood samples, the team first established the normal or reference range for the levels of porphyrin in cord blood red blood cells, a measure called total erythrocyte porphyrin (TEP). In full-term newborn cord blood, the TEP was 1.2-3.1 micromoles/L, which was higher than that of adult venous blood samples of less than 1.7 micromoles/L, the data showed.
The team then assessed TEP in cord blood samples from seven infants with EPP or XLP who had available clinical information. Among them, four had either no or small borderline blood porphyrin peaks. None of these children, some now adults, developed photosensitivity, the researchers noted.
Of the three remaining patients, one had a TEP of 21 micromoles/L and a marked increase in a type of porphyrin called metal-free protoporphyrin in red blood cells, consistent with a diagnosis of EPP.
Another patient had a TEP of 39 micromoles/L with elevations in both metal-free and zinc-bound protoporphyrin at birth. XLP was confirmed by genetic analysis weeks later. TEP in both of these patients increased over time, and both had acute light sensitivity.
The seventh patient had slightly higher TEP levels, mostly zinc-bound protoporphyrin, than the TEP reference range. The elevated TEP persisted at 4 months of age, but it did not increase, and he remained asymptomatic at the age of 18 months. Genetic analysis showed low activity in only one of his two FECH gene copies, each inherited from a biological parent, as the cause of EPP.
Based on these findings, the researchers recommended that cord blood, or red blood cell, porphyrins be tested to identify babies who, if given phototherapy for jaundice in the first weeks after birth, would be at risk of painful photosensitivity. The results of such testing would help clinicians adopt certain precautions should the infants need treatment for jaundice.
The team further suggested that “infants at risk of inheriting protoporphyria who have normal [red blood cell] porphyrin results at birth should be reinvestigated for protoporphyria if photosensitivity manifests clinically at an older age.”
“These cases are rare, … and management is challenging,” the researchers noted.
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