Correspondence

Pregnancy in a Patient with Congenital Erythropoietic Porphyria

N Engl J Med 2007; 357:622-623August 9, 2007

Article

To the Editor:

Congenital erythropoietic porphyria, a rare autosomal recessive disorder of heme biosynthesis, results from markedly deficient uroporphyrinogen III synthase activity.1,2 Data regarding pregnancy in patients with this condition are lacking, which may be explained by the rarity of the disease, as well as social restrictions due to associated photosensitivity or disfiguring effects in more severely affected patients. We describe a successful pregnancy in a patient with congenital erythropoietic porphyria.

The patient presented at 3 months of age with pink urine and severe photosensitivity; congenital erythropoietic porphyria was diagnosed on the basis of analysis of urinary, fecal, and blood porphyrin. Bone marrow transplantation, an established treatment option,3 was considered at the age of 18 months but was not pursued, owing to concerns about risks and the lack of a suitable donor. At the age of 9 years, in an attempt to suppress erythropoiesis and thus reduce the overproduction of porphyrin, hypertransfusion was initiated in combination with subcutaneous administration of deferoxamine but was discontinued because of its minimal efficacy. Analysis of the uroporphyrinogen III synthase gene identified Cys73→Arg and IVS8-23A→G mutations, a combination previously described in a patient moderately affected with congenital erythropoietic porphyria.4

At 19 years of age, our patient became pregnant. There were no antenatal complications. The plasma porphyrin level increased during the second trimester and fell during the third trimester (Figure 1Figure 1Plasma Porphyrin Levels during Pregnancy.), changes that were consistent with physiologic changes in erythropoiesis and fluid balance during pregnancy.5 At 39 weeks of gestation, elective caesarean section for breech presentation was performed under dimmed lights with minimal exposure of the patient's skin, without complication. A female infant with normal Apgar scores and birth weight of 3.52 kg was delivered. The plasma porphyrin level in the infant was 231 nmol per liter at the time of the birth (adult reference range, 0 to 11.2 nmol per liter) and decreased to 104 nmol per liter at 48 hours. No follow-up blood samples were available.

Teeth erupted when the infant was 6 months of age; they showed distal brown pigmentation, with a sharply defined margin — consistent with porphyrin staining — where calcification had occurred before birth in association with exposure to maternal porphyrin (i.e., erythrodontia) (Figure 2Figure 2Brown Staining of the Infant's Teeth.). This condition has been recognized in patients with congenital erythropoietic porphyria. The child has had normal development and no photosensitivity during 3 years of follow-up.

The severity of congenital erythropoietic porphyria correlates with the degree of residual uroporphyrinogen III synthase activity, with more activity resulting in less severe disease.1,2 The patient's early clinical presentation was assumed to indicate severe disease. In retrospect, the clinical course suggested a moderate clinical phenotype, confirmed by subsequent genotype studies. Cys73→Arg is the most frequently reported mutation in patients with congenital erythropoietic porphyria, accounting for one third of affected alleles,1,2 and leads to complete loss of function of uroporphyrinogen III synthase. In contrast, the IVS8-23A→G mutation occurs at a branch point, and some function is retained.3

The present case indicates that patients with congenital erythropoietic porphyria who are not severely affected may do well with conservative management and that successful pregnancy is possible in such patients.

Nirmala Hallai, M.R.C.P.
Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom

Alexander Anstey, F.R.C.P.
Royal Gwent Hospital, Newport NP20 2UB, United Kingdom

Shevaun Mendelsohn, F.R.C.P.
John Williams, F.R.C.O.G.
Gareth Evans-Jones, F.R.C.P.H.
Sadia Malick, M.B., B.S.
Countess of Chester Hospital, Chester CH2 1UL, United Kingdom

Michael N. Badminton, Ph.D., F.R.C.Path.
Cardiff University, Cardiff CF14 4XN, United Kingdom
mike.badminton@cardiffandvale.wales.nhs.uk

5 References

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