Congenital erythropoietic porphyria (Günther disease)

Severe deficiency of uroporphyrinogen III cosynthase (UROS)

In utero or shortly after birth: Severe cases manifesting as nonimmune hydrops

Soon after birth: Skin blistering, hemolytic anemia, hyperbilirubinemia, red urine, dark diapers that show a red fluorescence under UV light

Phototherapy for hyperbilirubinemia leads to severe skin blistering.

In adulthood: Facial disfiguration, increased hair growth, corneal scarring (possibly severe), hemolytic anemia, splenomegaly, erythrodontia, deposition of porphyrins in bone, bone demineralization (possibly substantial)

Porphyrins in plasma, urine, and stool elevated to levels higher than those in other porphyrias, with uroporphyrin I and coproporphyrin I the predominant porphyrins in urine and stool

Urinary ALA and PBG virtually normal

Can be confirmed by low RBC UROS activity (< 10%), but test not readily available

Genetic analysis of UROS gene, which reveals homozygous or compound heterozygous mutations on chromosome 10 (most common mutation is p. C73R)

For in utero diagnosis: Measurement of amniotic porphyrins or genetic analysis

Avoidance of sunlight (including lights for treating neonatal hyperbilirubinemia)

Use of sun-protective clothing

Iron reduction therapy

Avoidance of skin trauma

Prompt treatment of secondary bacterial infections to help prevent scarring

Splenectomy possibly beneficial for patients with hemolytic anemia

Hematopoietic stem cell transplantation potentially curative

Hepatoerythropoietic porphyria

Severe deficiency of uroporphyrinogen decarboxylase (UROD)

Early childhood

Skin blistering

Red urine

Anemia

Elevated isocoproporphyrin in stool and urine

Elevated zinc protoporphyrin in RBCs (to differentiate from PCT)

Confirmed by very low RBC UROD activity

Genetic analysis of UROD gene, which reveals homozygous or compound heterozygous mutations

Avoidance of sunlight

Phlebotomy possibly beneficial to patients with milder cases

Treatment of severe disease similar to that of congenital erythropoietic porphyria

Dual porphyria

Disorders resulting from deficiencies of 2 enzymes of the heme biosynthetic pathway

Clinical and biochemical manifestations of both disorders

In acute porphyrias: Neurovisceral symptoms triggered by porphyrogenic agents

In cutaneous porphyrias: Hypersensitivity to sunlight with blistering and fragile skin

Porphyrin and porphyrin precursor excretion patterns

Confirmed by family history and enzyme analyses

In acute porphyrias: Avoidance of triggering agents

In cutaneous porphyrias: Skin protection and avoidance of sunlight