Hepatoerythropoietic porphyria in a 2-year-old child: Clinical features and effects of treatment.

Hepatoerythropoietic porphyria (HEP) is a rare autosomal recessive disorder of heme biosynthesis caused by severe deficiency of uroporphyrinogen decarboxylase (UROD). It typically presents in infancy or early childhood with marked photosensitivity, skin fragility, blistering, dyspigmentation, hypertrichosis, and dark urine. We report a girl from Brazil who developed blistering and ulcerative lesions of the face and upper extremities beginning at 10 months of age, along with dark urine and gray discoloration of the teeth. She was 2.5 years old when first evaluated at the Massachusetts General Hospital Porphyria Center. Prior genetic testing in Brazil had already identified two UROD variants, c.239C>G (p.Ala80Gly) and c.464C>T (p.Ala155Val). At our center, erythrocyte UROD activity was markedly reduced to approximately 5% of normal, and plasma, urine, stool, and erythrocyte porphyrins were all substantially elevated, confirming the diagnosis of HEP. Erythrocyte protoporphyrin was 83.5% zinc-chelated. The patient also had persistent mild hepatosplenomegaly and mild transaminase elevation. Management included strict photoprotection and sequential trials of cholestyramine and cimetidine, followed by serial therapeutic phlebotomy while continuing cimetidine. Neither cholestyramine nor therapeutic phlebotomy was associated with clear biochemical improvement, whereas cimetidine was temporally associated with a decline in urinary porphyrins, although other biomarkers were more variable. This case highlights the importance of considering HEP in children with blistering lesions on sun-exposed skin.