Effects of Hematin in Hepatic Porphyria

Dhar, Gaurav; Bossenmaier, Irene; Petryka, Z.J.; Cardinal, Ruth; Watson, C. J.

doi:10.7326/0003-4819-83-1-20

Cited by 99 publications

(37 citation statements)

References 27 publications

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“…Each infusion was followed by a highly significant decline of serum ALA and PBG. This was soon confirmed in several case studies (11)(12)(13)(14) reported from this laboratory, the decline being regularly associated with rapid clinical remission. Nevertheless, in porphyria roster no.…”

supporting

confidence: 58%

“…The preparation of crystalline hemin and of the hematin solution (12) for infusion is to be described in detail elsewhere (1), also a recent, preferred manner of infusion. The latter is mentioned briefly in the following.…”

Section: Methodsmentioning

confidence: 99%

“…The tube is connected with a saline bottle, and when the infusion is complete, the system is flushed with saline prior to removal of the needle. In many infusions this technique has been unaccompanied by vein irritation or phlebitis, such as were encountered at times with the conventional method (12). The number of infusions and interval between has been related roughly to the "severity" class A, B, or C, as will be discussed elsewhere (1 (1).…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, in porphyria roster no. 430 (P430), one of PV, our first patient thus treated (12), hematin was deferred for 3 days pending a possible spontaneous, or glucose-induced improvement (15), but this was not observed, respiratory paralysis and quadriplegia persisting. Tracheostomy and assisted respiration were probably life-saving, but because the patient's status was still highly precarious, hematin was administered in two 250-mg infusions each day, at an interval of 2 days, for a total of 1 g. There was progressive improvement of the respiratory paralysis and slower return of function in the legs, with a permanent left peroneal palsy.…”

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confidence: 99%

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

Watson¹,

Pierach²,

Bossenmaier³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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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 copropor hyria. 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 6-aminolevulinic acid synthetase [6-aminolevulinate synthase; succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] in relation to inadequate heme, and repression by heme, stimulated early trials of hematin infusions to overcome the acute relapse in the foregoing inducible porphyrias. Recently this experience has been considerably expanded, 143 infusions of hematin having been given in 22 cases. Studies of the effect on the serum concentrations of 6-aminolevulinic acid and porphobilinogen have shown a highly significant decline, often to 0, especially of 6-aminolevulinic acid. A distinct relationship to the clinical severity of the attack has been evident in the frequency and magnitude of decline of serum 5-aminolevulinic acid and porphobilinogen. This was regularly associated with objective clinical improvement. The present preliminary report will consider briefly some basic and associated clinical aspects of the remission due to hematin, in cases of "inducible" hepatic porphyria. In a later paper this effect will be considered in greater detail (1).Those forms of hepatic porphyria in which various inducing factors are liable to precipitate a life-threatening acute neurologic relapse are appropriately grouped under the term inducible (1). This relates to 3-aminolevulinic acid synthetase [ALA-synthetase; 5-aminolevulinate synthase; succinyl-CoA: glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37], the rate-limiting enzyme of porphyrin and heme biosynthesis (2-6). The term inducible embraces the three autosomal dominant genetic errors, acute intermittent porphyria (AIP), porphyria variegata (PV), and hereditary hepatic coproporphyria (HC), but it does not include hepatic porphyria cutanea tarda, in which evidence of induction is slight or lacking (7, 8), as well as the neurologic symptoms of the acute attack in the inducible forms and the prominent excesses of porphyrin precursors, ALA and porphobilinogen (PBG) in liver, urine, and blood serum, increases of which are usually observed at least in the early symptomatic stage of the porphyric relapse. The inducible forms are characterized by derepression or impaired feedback regulation and secondary induction of hepatic ALA-synthetase (6) (see above). There is reason to believe that this is related to hepatic heme deficiency incident to the respective genetic (partial) lack of uroporphyrinogen synthetase in AIP (6), heme synthetase in PV (7), and coproporphyrinogenase in HC (9). Any one of these traits constitutes a partial block in heme synthesis, responsible, as already mentioned, for the negati...

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supporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Watson¹,

Pierach²,

Bossenmaier³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…Substrate compensation for this defect is not possible, however, because the activity of URO-S becomes rate-limiting with consequent accumulation of PBG and ALA (22). Since hematin feedback inhibits ALA synthetase, infusions of this compound have recently been used to treat acute attacks of AIP with successful clinical remission (23). The elevated plasma levels of both ALA and PBG were shown to return (6).…”

Section: Discussionmentioning

confidence: 99%

Catecholamine Uptake, Accumulation, and Release in Acute Porphyria

Beal¹,

Atuk²,

Westfall³

et al. 1977

J. Clin. Invest.

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A B S T R A C T Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither 8-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [3H]

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