The Treatment of Acute Intermittent Porphyria with Laevulose

1977 ◽  
Vol 53 (4) ◽  
pp. 365-371 ◽  
Author(s):  
M. J. Brodie ◽  
M. R. Moore ◽  
G. G. Thompson ◽  
A. Goldberg
Keyword(s):  
Acute Intermittent Porphyria ◽  
Acute Attack ◽  
Therapeutic Regimen ◽  
Porphobilinogen Deaminase ◽  
Mitochondrial Enzymes ◽  
Uroporphyrinogen Decarboxylase ◽  
Coproporphyrinogen Oxidase ◽  
Marked Diminution ◽  
Haem Biosynthesis ◽  
Cytosolic Enzymes

1. The activities of the enzymes of haem biosynthesis were studied in 23 patients with acute intermittent porphyria. The mitochondrial enzymes δ-aminolaevulinate synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes δ-aminolaevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase in erythrocytes. 2. Leucocyte δ-aminolaevulinate synthase activity was elevated (P < 0·001), with marked diminution of porphobilinogen deaminase activity (P < 0·001) and reduction in the activities of δ-aminolaevulinate dehydratase (P < 0·01) and uroporphyrinogen decarboxylase (P < 0·005). 3. A therapeutic regimen based on intravenous laevulose infusion was studied. In four patients in acute attack and one in remission laevulose treatment was associated with a fall in δ-aminolaevulinate synthase activity, a rise in porphobilinogen deaminase and uroporphyrinogen decarboxylase activities, and a fall in urinary porphyrin precursor excretion (P < 0·001). These studies provide a basis for the evaluation of the use of sugars in acute intermittent porphyria.

Alterations in the Activity of Enzymes of Haem Biosynthesis in Lead Poisoning and Acute Hepatic Porphyria

1977 ◽  
Vol 53 (4) ◽  
pp. 335-340
Author(s):  
B. C. Campbell ◽  
M. J. Brodie ◽  
G. G. Thompson ◽  
P. A. Meredith ◽  
M. R. Moore ◽  
...  
Keyword(s):  
Lead Poisoning ◽  
Haemoglobin Concentration ◽  
Acute Intermittent Porphyria ◽  
Normal Subjects ◽  
Uroporphyrinogen Decarboxylase ◽  
Coproporphyrinogen Oxidase ◽  
Hereditary Coproporphyria ◽  
Haem Biosynthesis ◽  
Significant Depression ◽  
Activity Of Enzymes

1. The activities of six of the enzymes of haem biosynthesis have been assayed in peripheral blood from patients with lead poisoning, acute intermittent porphyria or hereditary coproporphyria. 2. Compared with normal subjects the lead-poisoned subjects had highly significant depression of δ-aminolaevulinate dehydratase, coproporphyrinogen oxidase and ferrochelatase. 3. Lead-poisoned subjects had highly significant elevation of δ-aminolaevulinate synthase activity. 4. δ-Aminolaevulinate synthase activity was inversely related to the haemoglobin concentration. 5. Increased δ-aminolaevulinate synthase and decreased δ-aminolaevulinate dehydratase activity are also found in acute intermittent porphyria. 6. Increased δ-aminolaevulinate synthase, normal porphobilinogen deaminase and uroporphyrinogen decarboxylase and decreased coproporphyrinogen oxidase are found in both lead poisoning and hereditary Coproporphyria. 7. These enzyme changes explain the recognized patterns of porphyrins and porphyrin precursors in blood and urine in these conditions.

Protoporphyrinogen oxidase, porphobilinogen deaminase and uroporphyrinogen decarboxylase in variegate porphyria

1985 ◽  
Vol 13 (1) ◽  
pp. 203-204 ◽  
Author(s):  
P. N. MEISSNER ◽  
E. D. STURROCK ◽  
M. R. MOORE ◽  
P. B. DISLER ◽  
D. L. MAEDER
Keyword(s):  
Porphobilinogen Deaminase ◽  
Uroporphyrinogen Decarboxylase ◽  
Protoporphyrinogen Oxidase ◽  
Variegate Porphyria

scholarly journals Prophylactic Heme Arginate Infusion for Acute Intermittent Porphyria

2021 ◽  
Vol 12 ◽  
Author(s):  
Hung-Chou Kuo ◽  
Chia-Ni Lin ◽  
Yi-Fen Tang
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Acute Intermittent Porphyria ◽  
Porphobilinogen Deaminase ◽  
Attack Frequency ◽  
Weekly Administration ◽  
Clinical Counseling ◽  
Heme Arginate ◽  
Before And After

Objectives: This study aimed to evaluate the efficacy of long-term weekly prophylactic heme arginate (HA) infusions in reducing attack frequency and severity in female AIP patients.Methods: We report the results of five female AIP patients with frequent recurrent attacks (&gt;9/year) before and after institution of weekly prophylaxis with heme arginate (3 mg/kg body weight). All five cases had confirmed disease-associated mutations in the porphobilinogen deaminase gene, and all had received genetic and clinical counseling about AIP.Results: In the five included patients, average annual attack rate (AAR) in the year prior to HA prophylaxis was 11.82 (range 9.03–17.06), and average total HA usage was 32.60 doses (range: 13.71–53.13). After 2.58–14.64 years of HA prophylaxis, average AAR was reduced to 2.23 (range 0.00–5.58), and attack severity (i.e., doses required per attack) was reduced from 2.81 to 1.39 doses/attack. Liver and renal function remained stable during weekly administration of HA prophylaxis. The most common complications were port-A catheter-related events. No other complications or safety concerns occurred with long-term use of HA prophylaxis.Conclusion: Our study demonstrated women with AIP receiving weekly prophylactic HA infusions resulted in fewer episodes that required acute HA treatment while maintaining stable renal and liver function. Weekly prophylactic HA infusions effectively prevent frequent porphyric attacks and reduce attack severity.

scholarly journals Reversible splenial lesion syndrome (RESLES) due to acute intermittent porphyria with a novel mutation in the hydroxymethylbilane synthase gene

2020 ◽  
Author(s):  
xiaoqing li ◽  
fei han ◽  
qianlong chen ◽  
tienan zhu ◽  
yongqiang zhao ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Autosomal Dominant ◽  
Stop Codon ◽  
Novel Mutation ◽  
Acute Intermittent Porphyria ◽  
Porphobilinogen Deaminase ◽  
Autosomal Dominant Disorder ◽  
Splenial Lesion ◽  
Partial Deficiency ◽  
Reversible Splenial Lesion Syndrome

Abstract Background: Reversible splenial lesion syndrome (RESLES) is a clinico-radiological syndrome characterized by the presence of reversible lesions specifically involving the splenium of the corpus callosum (SCC). The cause of RESLES is unknown. However, infectious-related mild encephalitis/encephalopathy (MERS) with a reversible splenial lesion remains the most common cause of reversible splenial lesions. Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Result: In this study, we report a 20-year-old woman with AIP who presented with MRI manifestations suggestive of RESLES, she had a novel HMBS nonsense mutation, a G to A mutation in base 594, which changed tryptophan to a stop codon (W198*). Conclusion: To the best of our knowledge, this is only one published case of RELES associated with AIP.

Effects of Hexachlorobenzene Feeding and Iron Overload on Enzymes of Haem Biosynthesis and Cytochrome P450 in Rat Liver

1977 ◽  
Vol 53 (2) ◽  
pp. 111-115 ◽  
Author(s):  
M. Louw ◽  
A. C. Neethling ◽  
V. A. Percy ◽  
M. Carstens ◽  
B. C. Shanley
Keyword(s):  
Cytochrome P450 ◽  
Synergistic Effect ◽  
Progressive Increase ◽  
Decarboxylase Activity ◽  
Progressive Decrease ◽  
Uroporphyrinogen Decarboxylase ◽  
Time Intervals ◽  
Liver Cytochrome ◽  
Haem Biosynthesis ◽  
P450 Concentration

1. The effect of hexachlorobenzene feeding on liver δ-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P450 was studied at various time-intervals in siderotic and non-siderotic rats. 2. In the non-siderotic group hexachlorobenzene feeding led to a progressive decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in δ-aminolaevulinate synthase activity. Cytochrome P450 concentrations were above normal throughout but fell toward the end of the experiment. 3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in δ-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P450 concentration also rose but to a lesser extent than that in the non-siderotic rats. 4. Hexachlorobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P450 turnover.

scholarly journals Influence of Age and Gender on the Clinical Expression of Acute Intermittent Porphyria Based on Molecular Study of Porphobilinogen Deaminase Gene Among Swiss Patients

2001 ◽  
Vol 7 (8) ◽  
pp. 535-542 ◽  
Author(s):  
Macé M. Schuurmans ◽  
Xiaoye Schneider-Yin ◽  
Urszula B. Rüfenacht ◽  
Cécile Schnyder ◽  
Christoph E. Minder ◽  
...  
Keyword(s):  
Acute Intermittent Porphyria ◽  
Molecular Study ◽  
Porphobilinogen Deaminase ◽  
Clinical Expression ◽  
Age And Gender ◽  
And Gender

scholarly journals Molecular and Biochemical Studies of Acute Intermittent Porphyria in 196 Patients and Their Families

2002 ◽  
Vol 48 (11) ◽  
pp. 1891-1900 ◽  
Author(s):  
Raili Kauppinen ◽  
Mikael von und zu Fraunberg
Keyword(s):  
Diagnostic Accuracy ◽  
Aminolevulinic Acid ◽  
Clinical Manifestations ◽  
Acute Intermittent Porphyria ◽  
Reference Interval ◽  
Acute Attack ◽  
Fecal Excretion ◽  
Variant Form ◽  
Roc Curve Analysis ◽  
Biochemical Tests

Abstract Background: Acute intermittent porphyria (AIP) is a metabolic disease with clinical manifestations that mimic other abdominal, neurologic, or mental crises. We studied the diagnostic accuracy of current laboratory tests during an acute attack and in remission. Methods: Since 1966, we have studied all known Finnish AIP patients (n = 196) and their families (n = 45) and identified the porphobilinogen deaminase (PBGD) mutation in each family. Diagnoses or exclusions of AIP were based on clinical data (including family history), biochemical tests, and in 239 cases, mutation testing. We retrospectively evaluated the diagnostic accuracy of erythrocyte PBGD activity, urinary excretion of porphobilinogen (PBG) and δ-aminolevulinic acid, and urinary and fecal excretion of porphyrins in these patients. Results: Measurement of urinary PBG identified all 35 AIP patients studied during an acute attack. The mean excretion of PBG was 50-fold above the reference interval, although the intraindividual increases were modest (1.6- to 4.0-fold). In the mutation-screened population, urinary PBG analysis identified only 85% of 81 AIP patients studied during remission, but by ROC curve analysis it was nonetheless the best of the biochemical tests. It was increased ≤2-fold in 29% of healthy relatives. Erythrocyte PBGD activity was decreased in only 84% of AIP patients, with results within the reference interval mainly in the variant form of AIP; it was decreased in 23% of healthy relatives. Conclusions: Measurement of urinary PBG is the best biochemical test for AIP, although it is unspecific and does not distinguish AIP from other acute porphyrias. Because the acute increase in PBG is often modest, the medical history, signs, and symptoms must be evaluated carefully during an acute attack. In addition, because biochemical analyses often remain indeterminate in remission, mutation analysis is needed to exclude or confirm the diagnosis of AIP.

A case of previously undiagnosed acute intermittent porphyria in a 34-year-old primigravida with gestational diabetes mellitus

2017 ◽  
Vol 6 (2) ◽  
Author(s):  
Ivan Žebeljan ◽  
Veronika Anzeljc ◽  
Tamara Serdinšek ◽  
Faris Mujezinović
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Acute Intermittent Porphyria ◽  
Venous Catheter ◽  
Skin Lesions ◽  
Acute Attack ◽  
Toxic Metabolites ◽  
Severe Type ◽  
Prompt Diagnosis

Abstract Porphyrias are very rare and easily overlooked diseases in pregnancy. Among these eight known metabolic disorders, acute intermittent porphyria (AIP) is the most common and most severe type. An enzymatic alteration in the haem biosynthesis pathway causes liver overproduction of neurotoxic toxic metabolites, which cause attacks of acute neurovisceral symptoms, severe abdominal pain and/or skin lesions. Women with AIP can sometimes develop their first acute attack during pregnancy, and because the symptoms are unspecific, the diagnosis is difficult to obtain and often missed. However, prompt diagnosis of AIP during pregnancy is crucial as treatment can significantly improve the pregnancy outcome. The backbone of the therapy is food rich with carbohydrates, complemented by 20% glucose infusion and adequate pain control. We present a case of previously undiagnosed AIP in a 34-year primigravida, whose treatment was especially challenging due to co-existing gestational diabetes mellitus and problems with the central venous catheter.

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