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

Abstract

A woman aged 54 was studied because of a severe acute porphyric (neurologic) relapse with clinical and chemical findings characteristic of porphyria variegate. 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. The sister exhibited the protocoproporphyria of porphyria variegata, together with a large amount of fecal "x"9 porphyrin fraction, without demonstrable isocoproporphyrins. The brother had a uro-isocopro-type of porphyria in accord with the diagnosis of porphyria cutanea tarda, and quite at variance with the sister's findings. This occurrence of porphyria variegata and porphyria cutanea tarda in siblings is thus far unique. Certain hypotheses are considered in respect to genetic aspects of the differing porphyrias in this sib ing pair.Porphyria cutanea tarda (PCT) and porphyria variegata (PV) are now generally recognized as entirely independent forms of porphyria. The genetic character of the latter is overt, that of the former relatively occult. PV was first known and is still at times referred to as South African genetic porphyria; while PCT has commonly been designated as "symptomatic" or "acquired." Nevertheless, we have observed PCT in 27 of 67 members examined, in 11 families (C. J. Watson, K. Ahmed, I. Bossenmaier, and R. Cardinal, in preparation). The same study reveals many other instances of familial occurrence in the literature. In addition to the foregoing families, 74 "sporadic" cases of PCT, apparently nonfamilial, were represented in the same roster of 464 cases of porphyria of all types observed since 1938. The relative infrequence of familial in contrast to "sporadic" PCT has often been ascribed to low penetrance of an autosomal dominant gene, and the phenotypic manifestations to "revealing" factors, notably alcohol, estrogens, iron overload, immunologic disturbances, and certain others (G. Gulmen, R. Cardinal, I. Bossenmaier, Z. J. Petryka, and C. J. Watson, in preparation).The present report describes a sister and brother, the former studied first because of an almost fatal acute neurologic relapse related to chemically typical PV; the latter found to have outspoken chemical evidence of PCT with very mild cutaneous manifestations to which little attention had been given.CASE PROTOCOLS P430, female, 54, German-American ancestry. Admitted to Northwestern Hospital, Minneapolis, on November 16, 1971, in extremis, with quadriplegia, respiratory paralysis, and vagal involvement including marked tachycardia and laryngeal weakness. Further clinical details are to be described separately.The Watson-Schwartz test for porphobilinogen (1), carried out in the local hospital, was strongly positive, confirming the suspected diagnosis of acute porphyria.She was transferred to this hospital and unit because of profound respiratory difficulty for which a tracheostomy with assisted respiration became ne...

Large phlebotomy in variegate porphyria

“…by demands for haem based cytochrome P-450 enzymes for detoxification. The patient in this report deviates from previously studied individuals with PCT-VP dual porphyria [2][3][4][5] in the respect that her faecal porphyrin excretion, albeit deviating from normal, gave no indication of PCT (this was, in fact, the main reason for the later actualization of the VP diagnosis). It also deviates from these previous reports as the normal erythrocyte uroporphyrinogen decarboxylase activity indicated a sporadic type of PCT [11].…”

“…In these, a porphyrin decarboxylation defect, giving rise to the dermatological and hepatic condition of porphyria cutanea tarda (PCT), is coupled to an enzyme deficiency state connected with a neurological or a dermato-neurological type of porphyria, i.e. acute intermittent porphyria [1,2] or variegate porphyria (VP) [3][4][5][6].…”

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

“…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. This strengthens the concept of genetic heterogeneity in this kindred and supports the suggestion of a double heterozygosity, as proposed in the primary paper [Watson, C. J. et aL (1975) Proc. Nat.…”

“…Recently, a paper which appeared in these PROCEEDINGS (1) described an individual (P431) with chemically typical porphyria cutanea tarda (PCT), member of a porphyria family in which the index case (P430) was clearly one of porphyria variegata. Four additional members, P435, P447, P461, and P462, have clinically latent porphyria variegata, but characteristic chemical abnormalities, while 20 are negative for either porphyric trait.…”

Variegate Porphyria: Past, Present and Future

“…Therefore, stool analysis has a much higher diagnostic value than urine analysis. However, stool porphyrin excretion patterns consistent with both VP and PCT have been reported within the same families [22,23]. It has been proposed that bile porphyrin analysis may be more effective than fecal porphyrin measurement for the detection of latent VP [24], but this method is not readily applicable to extensive family studies.…”