Doss, Sixcl-Dietrich and Verspohl: "Glucose effect" in hepatocyte culture and in acute hepatic porphyrias 505 J. Clin. Chem. Clin. Biochem. Vol. 23, 1985, pp. 505-513 (Received January 26/May 8, 1985) Summary: The effect of glucose on drug-promoted induction of porphyrin synthesis was studied in chick embryo liver cell culture with and without the addition of exogenous -aminolaevulinic acid (ALA). Induction of ALA synthase was abolished by haemin or glucose. Less than 10% 0f porphobilinogen is converted into protoporphyrin. Protoporphyrin synthesis cannot be enhanced by high ALA concentrations. The conversion of exogenous ALA into porphyrins decreases with increasing concentrations of ALA from 0.1 to 2.0 mmol/1, whereas porphobilinogen accumulates, thus reflecting the rate limiting function of Uroporphyrinogen synthase, which is not influenced by glucose. This needle-eye-like function of Uroporphyrinogen synthase within the porphyrin biosynthetic chain explains the urinary increase of ALA and porphobilinogen in the acute phase of variegate and coproporphyria, similar to that in acute intermittent porphyria. i * The "glucose effect" was also investigated in vivo in humans in 32 courses of hereditary acute hepatic . v porphyrias (acute intermittent porphyria, variegate porphyria, coproporphyria and porphobilinogen synthase defect porphyria). Patients were treated with high carbohydrate intake (~500 g/24 h), mainly in the form of glucose infusions. There was a resulting coiisistent and highly significant decrease of porphyrin biosynthesis metabolites, accompanied by clinical improvement in most of the patients. "Glucose-Effeki" und limitierende Funktion der Uroporphyrinogen-Synthase auf den Porphyrinstoffwechsel in der Leberzellkultur in Bezug auf die akuten hepatischen Pörphyrien des MenschenZusammenfassung: Die Wirkung von Glucose auf die Arzneimittel-vermittelte Induktion der Porphyrinsynthese wurde in Hühnerembryo^Leberzellkulturen unter Bedingungen mit endogener und exogener 5-Aminolävulinsäüre (ALS) studiert. Die Induktion der ALS-Synthase konnte durch Hämin oder Glucose aufgehoben werden. Wenjger als 10% Porphobilinogen wird in Porphyrine konvertiert. Die Synthese von Protoporphyrin kann unter hohen ALS-Konzentrationen nicht gesteigert werden. Die Umwandlung exogener ALS in Porphyrine fällt mit steigender Konzentration der ALS von 0,1 bis 2,0 mmol/1, während Porphobilinogen akkumuliert: Hierin spiegelt sich die Umsatz-limitierende Funktion der Uroporphyrinogen-Synthase, die nicht durch Glucose beeinflußt wird". Die Nadelöhr-ähnliche Funktion der Uroporphyrinogen-Synthase innerhalb der Porphyrinbiosynthesekette erklärt den Anstieg von ALS und Porphobilinogen im Urin in der akuten Phase der Porphyria variegata und der Koproporphyrie, welcher demjenigen bei akuter intermittierender Porphyrie ähnlich ist.Der "Glucose-Effekt" in vitro wurde mit dem in vivo beim Menschen verglichen und bei 32 Verläufen hereditärer akuter hepatischer Porphyrieii untersucht (akute intermittierende Porphyrie, Porphyria varie...

The "glucose effect" was investigated in human acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria, coproporphyria and porphobilinogen synthase defect porphyria) and in avian liver cells. 8 patients (7 women) with acute abdominal-neurological porphyria syndrome and 3 patients (2 women) in the remission phase were treated with high carbohydrate intake (approximately 500 g/24 h), mainly in form of intravenous glucose infusions. The biochemical response with a decrease of metabolites of porphyrin biosynthesis was highly significant, accompanied by clinical improvement in 10 courses of 9 patients. Two patients with delayed detection of the disease under the condition of Landry paralysis died after temporary clinical improvement due to ventricular arrythmias in one case and septicemia in the other. The importance of early diagnosis and therapy, and omission of drugs and alcohol cannot be overemphasized. Complementary studies show the "glucose effect" in drug -mediated induction of porphyrin synthesis in liver cells grown in culture: delta-Aminolevulinic acid synthase and protoporphyrin synthesis are repressed.

Diabetic oral glucose tolerance test together with hyperinsulinemia in a patient with decompensated acute intermittent porphyria is contrasted to normal findings in compensated acute intermittent porphyria (AIP). Results point to the essential role of insulin for the depression of porphyrin precursor overproduction as a mediator of the "glucose effect".

No abstract

A patient is reported who developed the first symptoms of spinal motor neuron affection 20 years prior to his death at the age of 79. In the course of the disease dementia and spasticity of the legs occurred. The patient died of metastasizing carcinoma of the colon. The autopsy revealed amyloid angiopathy of the brain and cervical spinal cord, corresponding to the clinical symptomatology. So far, 11 cases of amyloid angiopathy have been reported in which dementia was preceded by dysarthric speech, ataxia and/or spasticity of the legs. We assume that these cases represent a distinct nosological entity, different from a variant course of Alzheimer's disease. The atypical symptomatology may cause problems in the diagnosis of amyloid angiopathy of the CNS.