Recovery from a variegate porphyria by a liver transplantation

Abstract

The porphyrias are a group of inherited or acquired enzymatic defects of heme biosynthesis. Each type of porphyria has a characteristic pattern of overproduction and accumulation of heme precursors based on the location of dysfunctional enzyme in the heme synthetic pathway. Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. A case of liver transplantation is described with a recovery from a variegate porphyria. Acute porphyria is commonly worsened by a wide variety of medications. We describe a step-by-step perioperative management protocol. (Liver Transpl 2004;10:935-938.) P orphyrias ( Fig. 1) are a group of genetic diseases usually with autosomic dominant transmission. They are characterized by a disorder of the heme synthesis owing to a defect of an enzyme involved in its production and leading to an accumulation of heme's precursors, the porphyrins, in some tissues and in the excreted matter (urine and feces). 1 Eighty percent of the heme synthesis takes place in the bone marrow, whereas 20% is hepatic and is involved in the P 450 cytochrome synthesis. Enzymatic defects are always incomplete; an absolute deficiency would be incompatible with life. Two groups of porphyrias are described-hepatic and erythropoietic-depending on the tissue in which the metabolic disorder predominates. All hepatic porphyrias, except porphyria cutanea tarda, produce acute neuro-visceral manifestations such as abdominal pain, and neurologic and psychiatric disorders. 2 The disease results from an overproduction of porphyrins in the liver. The accumulation of some porphyrins, in porphyria cutanea tarda and protoporphyria, is then responsible for the chronic hepatic disease. We report our experience with a recovery from a variegate porphyria (VP) by a liver transplantation. Case PresentationA 46-year-old man underwent a liver transplantation for a Child-Turcotte-Pugh B alcohol induced cirrhosis. His history included chronic alcohol abuse, with no alcohol intake for 1 year, with 1 episode of decompensated ascites and 2 episodes of spontaneous bacterial infections of the ascites fluid. When the patient was eligible for liver transplantation, blood tests were as follows: prothrombin time, 37 %; total serum bilirubin; 206m/L; platelets; 100,000/mL; albumin; 33g/L. He also experienced a VP progressing for 20 years that was responsible for abdominal pain and cutaneous manifestations (bullous skin eruption upon exposure to sunlight during a trip to Spain). Following an acute attack two years ago, the laboratory tests showed an increase in porphobilinogen in the urine to 13.2 m/L (normal, Յ5 m/L); an increase in total porphyrin in the feces, dry weight 230 nm/g (normal, Յ 200nm/g), mainly involving the protoporphyrins without involving coproporphyrin and uroporphyrin; and a total porphyrin concentration in the plasma (spectrofluorometric dosage) reaching the upper normal limit. An evaluation of the lymphocyte pr...

RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice

“…Although hemin is effective, it is slow to take effect and is associated with various side effects such as phlebitis, thrombosis, and iron overload (15). Recently, orthotopic liver transplantation has successfully treated several acute hepatic porphyria patients with recurrent and uncontrollable attacks (18)(19)(20), but it is associated with high morbidity and limited organ availability and should be reserved as a last-resort treatment. Thus, there is a clear need for a more effective, fasteracting, and safer therapy.…”

“…and incapacitating attacks resulted in the rapid normalization of ALA and PBG levels and the abrupt remission of attacks (18)(19)(20). Thus, the liver is the primary site of pathology in the acute hepatic porphyrias, and therapies designed to inhibit the induced overexpression of ALAS1 and the resulting elevation of ALA and PBG would prevent or treat the acute attacks in all four acute hepatic porphyrias.…”

Neurological Complications of Acute Intermittent Porphyria

“…Furthermore, it is possible that a porphyrogenic attack may result in a significant increase in circulatory ALA and PBG, causing vascular injury and impaired permeability, and affect regions that are particularly vulnerable to hypoxia-ischemia and excitotoxicity. In support of the purported link between increased (hepatic) ALA and PBG production and AIP is the finding that the several patients with severe AIP became asymptomatic after liver transplantation [13,14]. …”

Neurovisceral Porphyrias: What a Hematologist Needs to Know

“…6 A patient with a diagnosis of variegate porphyria, who underwent liver transplantation for alcoholic cirrhosis, similarly experienced biochemical improvement after liver transplantation. 9 In contrast, liver transplantation was not beneficial clinically or biochemically in a child with severe ALA dehydratase deficiency, suggesting that ALA overproduction did not arise chiefly from the patient's native liver.…”