6.2.4 Congenital Erythropoietic Porphyria (CEP)

Very rare. Symptoms (light sensitivity) starting early in life (<10 years of age); Incidence 0.1:100,000. Onset in adult life are milder variants.

Chronic disturbance of the hem-(porphyrin) biosynthesis in erythrocytes leading to accumulation of photosensitive porphyrins in the skin and other organs, clinically presenting blistering, chronic ulcers, and delayed healing and mutilation of light-exposed parts.

Hypersplenism, haemolytic anaemia with thrombocytopenia may occur.

Autosomal-recessive inherited biallelic mutation of the hem biosynthesis due to deficient activity of the fourth enzyme of the heme biosynthetic pathway, uroporphyrinogen III synthase, which is encoded by the uroporphyrinogen III synthase gene leading to accumulation of the non-physiologic porphyrinogen I isomers, uroporphyrinogen I and coproporphyrinogen I in bone marrow erythroid precursors and erythrocytes and in skin, teeth and internal organs. The isomer I porphyrinogens undergo auto-oxidation to the corresponding porphyrins, which are photo-activated.

Severely affected patients are transfusion-dependent throughout life, have secondary hypersplenism and significant cutaneous involvement, presenting as extreme light hypersensitivity, starting at birth. Blister formation and disfigurment due to scarring mutilations by UV light (“wolf children”). Hypertrichosis and poikiloderma. Risk of carcinoma development on scars. Red fluorescence of urine and red teeth (erythrodonty: brown teeth that fluoresce under Wood’s lamp (about 410 nm) illumination).

• Hepatic porphyrias: porphyria cutanea tarda (prototype): sporadic, genetic/familiar, toxic

• Erythropoietic porphyrias

  • Erythropoetic protoporphyria

  • Congenital erythropoetic porphyria (Günther)

Variegate porphyria and hereditary coproporphyria are acute porphyrias, which present with abdominal pain and skin manifestations as seen in porphyria cutanea tarda.

Determination of the defective enzymes and of uroporphyrinogen I in the urine (special laboratory). Red fluorescence of the urine and of teeth under Wood’s lamp (about 410 nm).

Secondary skin infections with subsequent bone resorption and photomutilation and scars, leading to loss of digits and facial profile. Secondary hypersplenism, haemolytic anaemia with thrombocytopaenia may occur.

Prevention: strict avoidance of sun and light exposure as well as erythrocyte transfusions to maintain the hematocrit >35; protection against visible light and long wave UVA.

Topical: Light protection (SPF/LSF > 30). Cave: Vitamin D-deficiency due to lack of vitamin-D production in the skin by UV.

Systemic: Bone marrow or hematopoietic stem cell transplantation is the only curative approach and has to be considered in a multidisciplinary approach.