A 4-year-old African American girl presented to the emergency department with a history of itching and a burning sensation in the palms and soles while playing at the beach on a sunny day. On examination, she had erythematous, minimally swollen palms and soles along with some facial puffiness. There were some hyperpigmented spots over the extremities and chest. Abdominal palpation revealed a palpable liver. Liver functions were noted to be abnormal with an aspartate aminotransferase 281 IU/L (reference range, 0-75 IU/L), alanine aminotransferase 408 IU/L (reference range, 0-40 IU/L) and gamma glutamyl transferase 444 (reference range, 0-60 IU/L), with a normal alkaline phosphatase and bilirubin. Her synthetic function was normal. An abdominal ultrasound survey revealed mild hepatomegaly. The hepatomegaly persisted, and her liver functions were still abnormal 4 months later. Studies for viral hepatitis, autoimmune hepatitis, Wilson disease, α-1-AT deficiency and hemochromatosis were negative. Special laboratories and the liver biopsy confirmed the clinical suspicion (Fig. 1).FIG. 1: (A) Liver histology H & E Staining reveals early modular fibrosis and dark brown pigment accumulation. (B) Bright red birefringent crystals with Maltese cross figures seem with polarization microscopy.What is the diagnosis? Hemochromatosis Protoporphyria Glycogen storage disorder Primary biliary cirrhosis ANSWER Protoporphyria. The fractionated urine porphyrin levels were normal, whereas the fractionated plasma porphyrins yielded high levels of protoporphyrins (1970 μg/L; normal range, 0.4 to 4.8 μg/L), suggestive of a ferrochelatase deficiency. Her liver biopsy (hematoxylin and eosin staining) revealed early nodular fibrosis and an accumulation of dark brown pigment in the canaliculi, connective tissue and Kupffer cells (Fig. 1). Examination of the pigment with polarization microscopy displayed bright red birefringent crystals with centrally located dark Maltese cross figures (Fig. 1). She was started on β-carotene, 30 mg per os twice a day, to improve photosensitivity, and ursodeoxycholic acid, cholestyramine and vitamin E to correct the liver dysfunction. Erythropoietic protoporphyria, also called "protoporphyria," is an inherited disorder of porphyrin-heme metabolism with cutaneous and systemic manifestations. Mutations in the genetic coding for ferrochelatase enzyme result in partial enzyme deficiency. Ferrochelatase (heme synthetase) catalyses the incorporation of ferrous iron into porphyrin to form heme. It can be transmitted as an autosomal dominant trait with variable penetrance and expressivity or as an autosomal recessive inheritance. Incidence is approximately 1 in 75,000 to 1 in 200,000 in some European populations (2). Photosensitivity is usually noticed during childhood. The liver dysfunction is related to protoporphyrin deposition in the liver. Affected patients are at risk for cholelithiasis. They generally do not have anemia or peripheral neuropathy. The hepatic manifestations may range from mildly disturbed liver functions in 20% to liver failure in less than 5% of the patients (3). The diagnosis is based on elevated protoporphyrin levels in erythrocytes and plasma. Fecal protoporphyrin is often elevated, but urinary porphyrin excretion is normal. Impending liver failure may be signaled by progressively rising levels of urinary protoporphyrin (2). Medical care involves counseling with lifelong photoprotection, limiting use of ethanol (alcohol excess has been implicated in fatal liver failure and may also increase photosensitivity), avoiding or using with caution agents that have cholestatic properties, especially estrogenic birth control pills. Do not curtail carbohydrate intake severely; a beneficial glucose effect may be modulating abnormal heme synthesis. Medical therapies to reverse liver disease have been inconsistently beneficial. Cholestyramine resin use can interrupt the enterohepatic recirculation of protoporphyrin to the liver, and bile salts can mobilize pigment directly from the liver. Liver transplantation is the last resort in irreversible liver damage, but it will not be protoporphyria curative (1).
Read full abstract
Dec 1, 2015
S I Kolesnikov + 4
Open Access