In two young patients with acute hepatic porphyria syndrome and persisting paralyses, which increased in intensity during intermittent occurring crisis, the activity of erythrocyte porphobilinogen synthase (delta-aminolevulinic acid dehydratase) was found to be considerably diminished, below 1% of the value of normal control persons. In contrast, the activity of uroporphyrinogen synthase was normal. Both patients have been excreting high quantities of delta-aminolevulinic acid and porphyrins in urine for years. Lead intoxication has definitively been excluded. Since the relatives also show lower activities in porphobilinogen synthase, the disease of these two patients is probably a new enzymatic type of inherited acute hepatic porphyria, the excretion profile of which is qualitatively completely different from those of the known acute porphyrias. The discovery of this porphyria confirms the theory of overlapping transition in the biochemical and clinical symptoms and analogies among acute hepatic porphyrias.

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Zusammenfassung: Die Uroporphyrinogen-Synthase (EC 4.3.1.8) wurde in den Erythrocyten von 380 Patienten bestimmt, unter denen sich 21 mit klinisch manifester akuter intermittierender Porphyrie befanden. Der Normalbereich einer Stichprobe lag bei 61 ± 23 μπιοΐ/ΐ · h (x ± 2s, n = 302) unter Einschlu der Aktivit ten der UroporphyrinogenCosynthase und der Folgeenzyme bzw. bei 65 ± 25 μιηοΐ/ΐ · h (x ± 2s, n = 274) nach Zerst rung der Uroporphyrinogen-Cosynthase und der Folgeenzyme durch Erhitzen des H molysates. Die Aktivit t der UroporphyrinogenSynthase bei Patienten mit akuter intermittierender Porphyrie betrug 35 ± 12 bzw. 40 ± 18 /umol/l · h und war damit signifikant (p < 0,001) gegen ber den Kontrollen erniedrigt. Bei den 21 F llen von akuter intermittierender Porphyrie war die Diagnose bereits aufgrund der charakteristischen Konstellation der Porphyrinvorl ufer-und Porphyrinausscheidung im Urin gestellt worden. Sowohl bei 7 der 21 F lle von akuter intermittierender Porphyrie als auch bei 6 Verwandten der Kranken lag die Aktivit t der Uroporphyrinogen-Synthase in der berlappungszone (40 bis 50 μηιοΐ/ΐ · h). Bei 32 Verwandten von 9 Patienten mit akuter intermittierender Porphyrie war die Aktivit t der Uroporphyrinogen-Synthase in 22 F llen signifikant erniedrigt, von denen 7 einen pathologischen Porphyrinvorl ufer-und Porphyrinbefund im Urin aufweisen. Die relative Aktivit t der Uroporphyrinogen-Synthase bei Patienten mit akuter intermittierender Porphyrie betrug 57%. Eine Erniedrigung der Uroporphyrinogen-Synthase-Aktivit t ber 30% gegen ber dem Mittelwert der Kontrollen ist ein sicheres Indiz f r das Vorliegen des prim ren enzymatischen Defektes bei Gentr gern f r akute intermittierende Porphyrie. Uroporphyrinogen synthase in erythrocytes in acute intermittent porphyria: new pathobiochemical aspectsSummary: Uroporphyrinogen synthase (EC 4.3.1.8) was determined in the erythrocytes of 380 patients, of which 21 showed clinical symptoms of acute intermittent porphyria. The normal range of a random sample was 61 ± 23 μιηοΐ/ΐ · h (x ± 2s, n = 302), including the activity of Uroporphyrinogen cosynthase and the subsequent enzymes; when all the latter enzymes were destroyed by heating the haemolysate, the normal range for Uroporphyrinogen synthase was 65 ± 25 /*mol/l · h (x ± 2s, n = 274). The respective activity of Uroporphyrinogen synthase in patients with acute intermittent porphyria was 35 ± 12, and 40 ± 18 μπιοΐ/ΐ · h which was significantly lower (p < 0.001) than the control values. In the 21 cases of acute intermittent porphyria, the diagnosis had already been made from the presence of porphyrin precursors and porphyrin in the urine. In 7 of the 21 cases of acute intermittent porphyria, and in 6 relatives of the patients, the activity of the Uroporphyrinogen synthase was in the overlap zone (40-50 jumol/l · h). 32 relatives of 9 of the patients with acute intermittent porphyria were investigated: 22 showed a significant decrease of Uroporphyrinogen synthase, and 7 of these showed pathological urinary porphyrin pr...

Two male patients aged 23 and 25 years with intermittent acute, frequently repeated porphyria syndromes presented an almost total deficiency of porphobilinogen-synthase [(PBG-S); synonym: delta-aminolevulinic acid dehydratase] in peripheral erythrocytes. PBG-S was investigated in bone marrow cells obtained by sternal puncture. A minimal enzyme activity of less than 3% of controls was established. Specific activity and protoporphyrin concentration decreased considerably during the course of erythropoiesis. Both patients are homozygous gene carriers; their parents (father and mother) as well as most of their brothers and sisters are heterozygotes with a PBG-S deficiency of approximately 50% of controls. All people with PBG-S deficiency are especially endangered by alcohol intake and lead exposure, because alcohol and lead toxically inhibit PBG-S.

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