Mortality in patients with acute intermittent porphyria requiring hospitalization: a United States case series.

Acute intermittent porphyria (AIP) is a genetic disorder in which patients may have life threatening attacks of neurologic dysfunction. This study examined the prognosis during the past 50 years of patients in the United States who required hospitalization for porphyric attacks. The cumulative survival was determined for 136 patients with AIP who were hospitalized for porphyric attacks between 1940 and 1988.

Liver transplantation in a patient with protoporphyria.

A 38-yr-old woman with liver disease due to protoporphyria underwent orthotopic liver transplantation. The resected liver was cirrhotic and contained a massive amount of protoporphyrin, with numerous birefringent pigment deposits. Transplantation was accomplished without difficulty following blood volume exchange to reduce the blood protoporphyrin level.

Red blood cell porphobilinogen deaminase in the evaluation of acute intermittent porphyria.

We measured the activity of the enzyme porphobilinogen deaminase in red blood cells of 222 persons. Ninety-seven of 107 patients with acute intermittent porphyria had enzyme activity below the normal range, whereas 55 of 56 patients with other types of porphyria had normal activity. This underscores the utility of this test in confirming the diagnosis of acute intermittent porphyria.

Pseudo-porphyria in a patient with hepatocellular carcinoma.

An elderly woman was found to have hepatocellular carcinoma and, incidental to this, markedly elevated levels of porphobilinogen in urine and serum. The delta-aminolevulinic acid levels in urine and serum were normal, but there was a distinct increase of porphyrins in urine and feces. Neither the patient nor her family gave a history suggestive of a clinical porphyria.

Hematin therapy in porphyric attacks.

We report our experience with hematin in the treatment of 57 patients in porphyric attacks. The ratio of acute intermittent porphyria: variegate porphyria: hereditary coproporphyria was 43:11:3. More than 90% of the patients showed not only a decline in their porphyrin precursors, but also a favor able clinical response.

Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission.

Transitory renal failure occurred in a patient with acute intermittent porphyria in clinical remission following i.v. administration of 1 000 mg hematin.

Effect of hematin in porphyric neuropathy.

Early, intravenous administration of hematin in a patient with acute intermittent porphyria and severe quadriparesis may have produced partial but remarkable improvement of neuropathy, and resulted in simultaneous decline of porphyrin precursors in the blood. Intermittent, biweekly hematin infusions given 1 month after the onset of the porphyric relapse had no effect on recovery of the residual neuropathy. We believe hematin may be effective in the treatment of porphyric neuropathy, if administered before irreversible neuronal damage has occured.

Comparison of the Hoesch and the Watson-Schwartz tests for urinary porphobilinogen.

A comparison of the Hoesch and the Watson-Schwartz tests shows that the latter, although slightly more complicated, generally yields more concise results and is superior in sensitivity and specificity for porphobilinogen. The recommendation of the Hoesch test for use as a "bedside screening" method seems unrealistic. Before the diagnosis of an "inducible" porphyria is made, a positive Hoesch test requires that indoles, indoleacetic acid, methyldopa, end-stage alcoholic malnutrition, and phenazopyridine HCl be excluded, to avoid misinterpretation.

Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias.

There is compelling, indirect evidence of hepatic heme deficiency due primarily to the respective genetic errors of the three inducible hepatic porphyrias, acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria. The induction is enhanced by exogenous inducers such as barbiturate, estrogens and other "porphyrogenic" chemicals and factors, including glucose deprivation. The newer knowledge of the induction of delta-aminolevulinic acid synthetase [delta-aminolevulinate synthase; succinyl--CoA:glycine C-succinyltransferase (decarboxylating), EC 2.

Porphyria variegata and porphyria cutanea tarda in siblings: chemical and genetic aspects (addendum).

A porphyria kindred in which the index case has porphyria variegata had also been shown to include a case of porphyria cutanea tarda, typical both from chemical and clinical features. The possibility that this was purely acquired rather than genetic seemed unlikely, but could not be wholly excluded. Recently, a niece of both of these cases, although asymptomatic, has been found to conform chemically with porphyria cutanea tarda, including the excretion of the isocoproporphyrin series, and thus represents the second case of this form of porphyria in this family.

Hematin treatment of acute porphyria. Early remission of an almost fatal relapse.

Intravenous infusions of hematin in a young woman with acute porphyria in profound relapse was followed within 48 hours by remission of symptoms and rapid recovery. From a state of severe central and peripheral nervous-system involvement, the patient recovered so completely that she was able to leave the hospital in less than a month, with only a residual weakness of her arms. Serial studies of serum and urinary levles of porphyrin precursors and serum level of hematin provided highly important information about the effect of hematin on acute porphyria.

The activities of uroporphyrinogen synthetase and cosynthetase in congenital erythropoietic porphyria (CEP).

Normal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes.

Porphyria variegata and porphyria cutanea tarda in siblings: chemical and genetic aspects.

A woman aged 54 was studied because of a severe acute porphyric (neurologic) relapse with clinical and chemical findings characteristic of porphyria variegata. During a family survey, her brother, aged 59, was found to have chemical abnormalities typical of porphyria cutanea tarda, without suggestion of neurologic manifestations. He had mild skin changes compatible with either of these forms of porphyria.

Effects of hematin in hepatic porphyria. Further studies.

The present study was carried out in five cases of hepatic porphyria, including three of acute intermittent porphyria, one of variegate porphyria, and one of porphyria cutanea tarda in clinical remission. In two cases of acute intermittent porphyria (in relapse), a marked lowering effect on serum and urine porphobilinogen and delta-aminolevulinic acic was observed, together with prompt and gratifying clinical improvement. In a third case, in chemical remission but with longstanding psychoneurosis, no significant effects were noted, nor were any observed in the case of porphyria cutanea tarda.

Repression by hematin of porphyrin biosynthesis in erythrocyte precursors in congenital erythropoietic porphyria.

Hematin administered intravenously in a patient with congenital erythropoietic porphyria evidently entered erythrocyte precursors in the bone marrow, producing the well-known negative feedback repression of porphyrin biosynthesis with marked decline of porphyrin concentrations in urine, circulating plasma, and erythrocytes. A delay in the major segment of this effect corresponded roughly with the sum of the average transit times through the maturation compartments of the erythrocyte precursors. This delay was considerably longer than previously observed in the decline of porphyrin precursors after administration of hematin in patients with hepatic porphyria.

Repression of the overproduction of porphyrin precursors in acute intermittent porphyria by intravenous infusions of hematin.

In a patient with a severe attack of acute intermittent porphyria, hematin given intravenously caused marked diminution of serum delta-aminolevulinic acid and porphobilinogen. The decline of aminolevulinate was more rapid than that of porphobilinoge. After 2 days of hematin administration, about 5 days were required for delta-aminolevulinic acid, and 11 days for porphobilinogen to return to the concentrations that were detected before treatment.