Porphyria variegata andporphyria cutanea tardainsiblings: Chemical andgenetic aspects (protocoproporphyria/uro-isocoproporphyria/"x" porphyrin/double heterozygosity)

Awomanaged54wasstudied because ofa severe acute porphyric (neurologic) relapse with clinical and chemical findings characteristic ofporphyria variegate. Dur- ingafamily survey, herbrother, aged59,wasfound tohave chemical abnormalities typical ofporphyria cutanea tarda, without suggestion ofneurologic manifestations. Hehad mildskin changes compatible witheither ofthese forms of porphyria. Thesister exhibited theprotocoproporphyria of porphyria variegata, together withalarge amount offecal "x"9 porphyrin fraction, without demonstrable isocopropor- phyrins. Thebrother hadauro-isocopro-type ofporphyria in accord withthediagnosis ofporphyria cutanea tarda, and quite atvariance withthesister's findings. Thisoccurrence ofporphyria variegata andporphyria cutanea tarda insib- lings isthus farunique. Certain hypotheses areconsidered in respect togenetic aspects ofthediffering porphyrias inthis sibingpair. Porphyria cutanea tarda (PCT)andporphyria variegata (PV)arenowgenerally recognized asentirely independent forms ofporphyria. Thegenetic character ofthelatter is overt, that oftheformer relatively occult. PV wasfirst knownandisstill attimes referred toasSouth African ge- netic porphyria; while PCThascommonly beendesignated as"symptomatic" or"acquired." Nevertheless, wehaveob- served PCTin27of67members examined, in11families (C.J.Watson, K.Ahmed, I.Bossenmaier, andR.Cardinal, inpreparation). Thesamestudy reveals manyother in- stances offamilial occurrence intheliterature. Inaddition to theforegoing families, 74"sporadic" cases ofPCT,appar- ently nonfamilial, wererepresented inthesameroster of 464cases ofporphyria ofall types observed since 1938. The relative infrequence offamilial incontrast to"sporadic" PCThasoften beenascribed tolowpenetrance ofanautoso- maldominant gene, andthephenotypic manifestations to "revealing" factors, notably alcohol, estrogens, ironover- load, immunologic disturbances, andcertain others (G.Gul- men,R.Cardinal, I.Bossenmaier, Z.J.Petryka, andC.J. Watson, inpreparation). Thepresent report describes asister andbrother, thefor- merstudied first because ofanalmost fatal acute neurologic relapse related tochemically typical PV;thelatter found to haveoutspoken chemical evidence ofPCTwithverymild cutaneous manifestations towhich little attention hadbeen given.