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M Doss

Publications and source records attributed to M Doss.

At least 73 records · Page 4Linked to original sources
PubMed1984

Lead poisoning in inherited delta-aminolevulinic acid dehydratase deficiency.

delta-Aminolevulinic acid dehydratase (ALA-D), respectively porphobilinogen synthase, EC 4.2.1.24) activity can be lowered by toxic, metabolic and hereditary factors. A 30-year-old painter was suffering from lead poisoning with an acute abdominal-neurologic syndrome and anemia. Blood lead was measured at 414 micrograms/l. Urinary ALA and coproporphyrin excretion as well as erythrocyte protoporphyrin had increased extremely, whereas ALA-D activity in erythrocytes had decreased extremely to 8% of controls. Excretion parameters, protoporphyrin, hemoglobin and lead returned to normal after treatment, but four years later ALA-D activity still remained diminished (30% of controls). An inherited enzyme deficiency was assumed and found in the mother, analogous to the subnormal ALA-D activity in heterozygotes of four other families. The inherited enzyme deficiency sensitized the patient to lead exposure and intoxication, which is a toxogenetic disease in this case.

Adult↗
PubMed1984

Development of chronic hepatic porphyria (porphyria cutanea tarda) with inherited uroporphyrinogen decarboxylase deficiency under exposure to dioxin.

Exposure to dioxin triggered a clinically manifest chronic hepatic porphyria (porphyria cutanea tarda) in two patients (brother and sister) with hereditary uroporphyrinogen decarboxylase deficiency. The patients showed a decrease of erythrocyte uroporphyrinogen decarboxylase activity to approximately 50% of controls even in reinvestigations after three years, whereas clinical symptoms and porphyrinuria had improved considerably. Only a subclinical phase of chronic hepatic porphyria persisted. Subnormal uroporphyrinogen decarboxylase activity could be determined in altogether nine family members. The remission of porphyria cutanea tarda into a subclinical phase occurred after chloroquine therapy. Subclinical phases of chronic hepatic porphyria (type A) in other family members remitted without special therapy. Among the 60 persons dioxin-exposed by the Seveso accident, a secondary coproporphyrinuria was found in 22% of examined patients with transition to a subclinical chronic hepatic porphyria in 5 cases. The changes had subsided completely after one year. A persistence of the transition state in 3 cases is probably due to alcohol influence. None of these cases developed a porphyria cutanea tarda. The investigations showed that a hereditary disposition is necessary for biochemical and clinical expression of chronic hepatic porphyria after a unique dioxin exposure. This is not given in the sporadic cases: after a unique dioxin exposure they indeed develop a symptomatic disturbance of porphyrin metabolism but not a clinically relevant chronic hepatic porphyria. We conclude that a unique acute exposure to dioxin can trigger the chronic hepatic porphyria disease process in persons with an underlying genetic abnormality of uroporphyrinogen decarboxylase.

Adult↗
PubMed1983

[Notes on porphyria].

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5-Aminolevulinate Synthetase↗
PubMed1983

Porphobilinogen-synthase (delta-aminolevulinic acid dehydratase) deficiency in bone marrow cells of two patients with porphobilinogen-synthase defect acute porphyria.

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.

Acute Disease↗
PubMed1982

Persistent protoporphyrinemia in hereditary porphobilinogen synthase (delta-aminolevulinic acid dehydrase) deficiency under low lead exposure. A new molecular basis for the pathogenesis of lead intoxication.

For several years, a 4-12-fold increase of the upper normal limit in erythrocyte protoporphyrin concentrations persisted in two men 34 and 39 years of age who were chronically exposed to lead. We are dealing with a zinc protoporphyrinemia in both cases, without lead intoxication or anemia. The 34-year-old had been a regular blood donor for 10 years and had already been treated for iron deficiency several times. Hemoglobin, red cell counts, hematocrit, and iron were at the lower normal limit. The activity of porphobilinogen synthase (PBG-S), uroporphyrinogen-synthase and -decarboxylase as well as urinary porphyrin precursors and porphyrin excretion were normal. Protoporphyrinemia was said to be due to a prelatent/latent iron deficiency. In the 39-year-old, the activity of PBG-S was lowered to 388 mumol/1 . h, as compared to the mean of controls (1,190 +/- 210, x +/- SD, n = 50), in connection with a slightly elevated excretion of delta-aminolevulinic acid and coproporphyrin in the urine and a high-normal blood lead level. In his family there was no history of either a protoporphyrinemia or a hematological disturbance. Six of eight family members in three generations showed a diminished activity of PBG-S: 600 +/- 160, P less than 0.001 compared to controls. These family members are heterozygous with regard to the PBG-S deficiency; they are clinically unobtrusive in comparison to homozygotes with an acute prophyria syndrome. Activation by zinc and reactivation by dithiothreitol were normal in contrast to PBG-S from patients with lead intoxication. The cause of biochemical symptoms of subclinical lead intoxication developed by the propositus is probably due to the hereditary PBG-S deficiency which sensitizes him to low-level lead exposure. The determination of red cell PBG-S activity can be recommended as a test detecting heterozygotes. The hereditary PBG-S deficiency is recognized as a new molecular basis for the pathogenesis of lead intoxication.

Adult↗
PubMed1982

[Hereditary coproporphyria (author's transl)].

A 28-year-old female was admitted to intensive medical care as an emergency with tetraplegia and respiratory paralysis. Acute hepatic porphyria of the hereditary coproporphyria type was diagnosed which was associated with epilepsy in the history. The polysymptomatology could be traced back for 12 years. From the spectrum of 46 wrong diagnoses a three-dimensional symptom complex of abdominal, neuropsychiatric and cardiovascular complaints and findings could be documented. The patient was ill for a total of more than 128 weeks, had been admitted to 14 different hospitals on 21 occasions and had undergone repeated surgery without improvement of her complaints. Porphyria diagnostics had not been considered previously.

Acute Disease↗
PubMed1982

Acute lead poisoning in inherited porphobilinogen synthase (delta-aminolevulinic acid dehydrase) deficiency.

The second enzyme of the porphyrin and heme synthesis pathway, porphobilinogen synthase (EC 4.2.1.24), can be lowered due to a hereditary defect or toxic damage. Lead is the most common cause for a toxically lowered activity. We report on a 48-year-old patient with an acute abdominal syndrome, anemia and a grave toxic disorder of porphyrin metabolism which was diagnosed as acute lead intoxication. Although the hematologic findings and porphyrins in the blood, as well as porphyrin precursors and porphyrin excretion in the urine, returned to normal within five months after exacerbation of the acute symptoms the activity of porphobilinogen synthase showed only 50% physiologic activity of healthy subjects six years after the acute syndrome with complete normalization of prophyrin metabolites and lead levels in blood and urine. The influence of alcohol was excluded. Enzyme activation by zinc and reactivation by dithiothreitol lies within the normal range and thus contradicts an increased body burden of lead. In connection with findings of a familiar porphobilinogen synthase defect we are most likely dealing with a hereditarily determined enzyme deficiency in this patient which sensitizes him to a lead intoxication.

Abdomen, Acute↗
PubMed1982

New type of acute porphyria with porphobilinogen synthase (delta-aminolevulinic acid dehydratase) defect in the homozygous state.

In two male patients with acute hepatic porphyria and persisting paralysis which increased in intensity intermittently, the activity of porphobilinogen synthase (PBG-S; delta-aminolevulinic acid dehydr(at)ase) was diminished in peripheral erythrocytes and bone marrow cells below 3% of normal controls. In contrast, the activities of uroporphyrinogen synthase and decarboxylase were normal. Both patients have been excreting high quantities of delta-aminolevulinic acid and porphyrins in urine for years. Lead intoxication and tyrosinemia could definitely be excluded. There was no experimental evidence for the existence of an inhibitor to PBG-S in urine, serum and erythrocytes from these two patients. The PBG-S deficiency was confirmed after DEAE cellulose chromatography: the concordance of relative and specific activity before and after chromatography of PBG-S from patients and controls differs from the findings in lead poisoning. A mutation of PBG-S probably at the level of the structural gene is concluded as the molecular basis of the inherited PBG-S defect porphyria. Since the relatives also show lower activities of PBG-S (approximately 50% of controls), the disease of these two patients represents 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 signs and clinical symptoms as well as analogies among the acute hepatic porphyrias and lead poisoning.

Adult↗
PubMed1981

The "glucose effect" in acute hepatic porphyrias and in experimental porphyria.

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.

Acute Disease↗