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Description of a New Mutation in Hepatoerythropoietic Porphyria and Prenatal Exclusion of a Homozygous Fetus
Cécile Ged, MD, PhD;
D. Ozalla, PhD;
C. Herrero, MD;
M. Lecha, MD;
M. Mendez, PhD;
H. de Verneuil, MD, PhD;
J. M. Mascaro, MD
Arch Dermatol. 2002;138:957-960.
Background Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous
porphyria, characterized biochemically by an increased urinary excretion of
polycarboxylated porphyrins. The disease is the result of a profound deficiency
(<10% of normal activity) of uroporphyrinogen decarboxylase (UROD) activity.
Hepatoerythropoietic porphyria is inherited as an autosomal recessive trait,
whereas familial porphyria cutanea tarda is dominant. At least 30 different
mutations of the UROD gene have been identified in
patients with HEP and familial porphyria cutanea tarda, with 1 predominant
missense mutation (glycine–to–glutamic acid substitution at codon
281) in Spanish patients with HEP.
Observation A 5-year-old patient with first-degree–related parents presented
with HEP and mild symptomatology. We found low levels of UROD enzymatic activity
and a new homozygous mutation of the UROD gene, a
phenylanine-to-leucine substitution at codon 46 (F46L). Both parents were
healthy carriers of the mutation. The mother had reduced UROD activity (50%
of normal), whereas the father had normal UROD activity. Prokaryotic expression
of the F46L mutation using a pGEX vector has been used to confirm the deleterious
effect of the mutation. When the mother started a new pregnancy, a prenatal
study showed the absence of F46L mutation in the fetus and no accumulation
of porphyrins in the amniotic fluid.
Conclusions A new mutation in the UROD gene causes a mild
HEP phenotype. A normal UROD enzymatic activity was observed in the father,
despite the presence of the heterozygous mutation. To our knowledge, this
observation is the first description of a prenatal exclusion of HEP.
From the Laboratoire de Pathologie Moléculaire et Thérapie
Génique, Université Victor Segalen-Bordeaux 2, Bordeaux, France
(Drs Ged, Mendez, and de Verneuil); and the Department of Dermatology, Hospital
Clinic, University of Barcelona, Barcelona, Spain (Drs Ozalla, Herrero, Lecha,
and Mascaro).
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