Severe Case of Rare Porphyria, CEP, Diagnosed in Newborn

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by Steve Bryson, PhD |

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A rare and severe form of porphyria — congenital erythropoietic porphyria (CEP) — was diagnosed in an infant girl immediately after birth.

The case report, “Perinatal onset of severe congenital erythropoietic porphyria,” was published in the journal Archives of Disease in Childhood: Fetal & Neonatal.

Porphyrias are a group of inherited disorders characterized by disruptions in the production of heme, an essential molecule that helps transport oxygen throughout the body.

CEP, also known as Günther disease, is the rarest type of porphyria. It is mainly caused by mutations in the UROS gene, which carries instructions for making uroporphyrinogen III synthase, one of the enzymes needed for making heme.

This enzyme’s deficiency or lack leads to the toxic buildup of porphyrins and other heme precursor molecules. Primarily seen in infants, a hallmark of CEP is severe light sensitivity, which can causing skin blistering and subsequent infections.

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In more severe cases, symptoms can include low red blood cell counts, a condition also known as anemia. Some patients need regular blood transfusions to maintain adequate red blood cell numbers.

Researchers at the Public Assistance Hospitals of Marseille, in France, described the case of newborn girl who was diagnosed with CEP soon after her birth.

She was born full-term to a healthy young couple of Caucasian ethnicity, and admitted to the neonatal intensive care unit with acute respiratory distress — a type of respiratory failure characterized by rapid onset inflammation and fluid buildup in the lungs.

A prenatal ultrasound performed at the 25th week of pregnancy revealed the girl had a pocket of fluid at the back of her neck (nuchal translucency) and her heart was abnormally enlarged (myocardial hypertrophy). Further examination, including a type of DNA analysis, failed to identify a cause for these symptoms.

She had multiple bruises at birth, an overall grey skin color, and her urine was reddish.

Blood tests showed she had low levels of red blood cells, white blood cells, and platelets. She also had high levels of lactate dehydrogenase, a marker of tissue damage, and abnormal liver function.

A bone marrow biopsy was then performed, as physicians suspected she might have macrophage activation syndrome, a condition caused by the excessive activation of certain immune cells.

However, tissue analysis revealed the presence of dark red porphyrin deposits. Further examination of urine and blood samples also showed the presence of high levels of porphyrins, the hallmark feature of porphyrias.

A detailed DNA analysis then revealed she had a mutation in both copies of the UROS gene, one inherited from each parent, confirming the diagnosis of CEP.

The identified mutation (p.Cys73Arg), which accounts for more than a third of CEP cases, led to the replacement of the amino acid cysteine for the amino acid arginine at position 73 of the protein sequence. (Amino acids are protein building blocks.)

Past studies have shown that a cysteine at position 73 is not necessary for the enzyme’s activity. Yet, a change to arginine at this particular position accelerates the unfolding and clumping of the protein.

Individuals carrying this mutation can experience severe disease manifestations, ranging from fluid buildup and death before birth, to severe anemia.

“In this extremely rare case, a bone marrow transplantation is considered before [she is] 1 year old as it is the only curative treatment of severe cases,” the researchers wrote.