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Porphyria Educational Services


PORPHYRIA EDUCATIONAL SERVICES BULLETIN
Vol. 2 No. 18 April 30, 2000
FOCUS: CONGENITAL ERYTHROPOIETIC PORPHYRIA [CEP]

Congenital Erythropoietic Porphyria better known as CEP or
Gunther's Disease is also known as Erythropoietic Porphyria; Congenital Porphyria;
Congenital Hematoporphyria; and/or Erythropoietic Uroporphyria.

CEP is an autosomal recessive, rare, and usually severe disorder
resulting from a deficiency of uroporphyrinogen III cosynthase.

At the close of 1999 there were fewer than 200 cases of
congenital erythropoietic porphyria that had been reported.

In CEP there is no clear racial or sexual predominance.

CEP porphyria occurs rarely in animals and that is mostly in cattle.
However it does appear in fox squirrels. According to a notation in the
Merck medical book, all fox squirrels have this condition but it does not
appear to affect them adversely,even though porphyrins are markedly increased.

The pathogenesis of CEP lies with the uroporphyringen III cosynthase gene.
Many different mutations of the human uroporphyrinogen III cosynthase gene
have been identified. Most patients have unrelated parents and have inherited a
different mutation from each. It is interesting in CEP that residual cosynthase
activity persists even in the most severe cases.

In CEP excess porphyrins accumulate in bone marrow mostly at the
stage of erythroid cell maturation, when hemoglobin synthesis is most active.

The symptomology of CEP includes skin blistering which is usually severe,
and begins soon after birth. The skin blistering is usually accompanied by
anemia and red urine. Some cases are relatively mild with onset of symptoms
in adult life. Severity depends on the mutations found in each patient and the
degree of enzyme deficiency.

Skin changes are similar to those of PCT but are usually more severe.
Blistering of sun-exposed skin often leads to scarring, infection, and loss
of facial features and fingers. Pigmentation changes and hypertrichosis are common.
Corneal scarring can be severe. Porphyrins are deposited in the
teeth (producing a reddish brown color termed erythrodontia) and in bone.

In CEP bone demineralization can be substantial. Some anemia and
splenomegaly are almost always present in CEP porphyrics.

Drugs, hormones (other than endogenous erythropoietin), and nutrition
(other than vitamin deficiencies that can impair the bone marrow) have
little influence on the CEP porphyria.

In CEP there are no neurologic manifestations.

The diagnosis of CEP is suggested by the presence of pink to dark brown
urine and/or the onset of severe photosensitivity in infancy and in rare cases
in adults.

Porphyrins are increased in bone marrow, erythrocytes, plasma, urine, and
feces in a characteristic pattern, usually to levels much higher than those in
other porphyrias.

Uroporphyrin I and coproporphyrin I are the predominant porphyrins in urine,
plasma, and erythrocytes, and coproporphyrin I is the predominant porphyrin in feces.
Sometimes erythrocytes contain large amounts of protoporphyrin, as in other
homozygous porphyrias.

Demonstration of deficient uroporphyrinogen cosynthase activity confirms the
diagnosis. ALA and PBG are not increased. Hepatoerythropoietic porphyria
is similar clinically, but porphyrin patterns are different.

Treatments for CEP are not very effective. Therefore, avoiding sunlight and
wearing protective clothing are important. Several manufacturers specialize in
protective fabrics and clothing for sun-sensitive people. More recently NASA has
developed a special space suit for CEP patients to wear.

Heterozygotes can be detected in affected families, and diagnosis in utero is possible.
Therefore, there are options for preventing genetic transmission.