Recombinant porphobilinogen deaminase targeted to the liver corrects enzymopenia in a mouse model of acute intermittent porphyria

2022 ◽  
Vol 14 (627) ◽  
Author(s):  
Karol M. Córdoba ◽  
Irantzu Serrano-Mendioroz ◽  
Daniel Jericó ◽  
María Merino ◽  
Lei Jiang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acute Intermittent Porphyria ◽  
Porphobilinogen Deaminase ◽  
Motor Neuropathy

Systemic and subcutaneous rApoAI-PBGD therapy protects against porphyrin precursor accumulation, pain, and motor neuropathy in AIP mice.

scholarly journals Acute Intermittent Porphyria: A Report of 3 Cases with Neuropathy

2019 ◽  
Vol 11 (1) ◽  
pp. 32-36
Author(s):  
Mohammed Alqwaifly ◽  
Vera Bril ◽  
Dubravka Dodig
Keyword(s):  
Biosynthetic Pathway ◽  
Metabolic Disorders ◽  
Case Series ◽  
Acute Intermittent Porphyria ◽  
Genetic Mutation ◽  
Nerve Conduction Studies ◽  
Porphobilinogen Deaminase ◽  
Motor Neuropathy ◽  
Clinical Presentations ◽  
Associated Symptoms

The porphyrias are metabolic disorders due to a defect in the heme biosynthetic pathway. Patients have diverse clinical presentations with neuropathy being frequent in acute intermittent porphyria (AIP). Associated symptoms are abdominal pain and seizures. Three patients presenting with neuropathy were later diagnosed with AIP on the basis of clinical features, erythrocyte porphobilinogen deaminase activity, neuropathic patterns, and nerve conduction studies. Testing for the HMBS genetic mutation confirmed the diagnosis of AIP in 1 patient. The findings from this case series confirm that porphyric neuropathy in AIP is a predominantly motor neuropathy with differing neuropathic presentations ranging from focal motor neuropathy to quadriplegia and respiratory failure.

scholarly journals Adenoviral-mediated expression of porphobilinogen deaminase in liver restores the metabolic defect in a mouse model of acute intermittent porphyria

2004 ◽  
Vol 10 (2) ◽  
pp. 337-343 ◽  
Author(s):  
Annika Johansson ◽  
Grzegorz Nowak ◽  
Christer Möller ◽  
Pontus Blomberg ◽  
Pauline Harper
Keyword(s):  
Mouse Model ◽  
Acute Intermittent Porphyria ◽  
Porphobilinogen Deaminase ◽  
Metabolic Defect

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 (>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.

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

Variant acute intermittent porphyria in a child

1990 ◽  
Vol 36 (5) ◽  
pp. 812-814 ◽  
Author(s):  
N R Badcock ◽  
G D Zoanetti ◽  
D A O'Reilly ◽  
E F Robertson
Keyword(s):  
Family History ◽  
Parenteral Nutrition ◽  
Enzyme Activities ◽  
Clinical Symptoms ◽  
Acute Intermittent Porphyria ◽  
Normal Activity ◽  
Porphobilinogen Deaminase ◽  
Acute Porphyria ◽  
Protoporphyrinogen Oxidase ◽  
History Of

Abstract A child who was grossly malnourished and who showed increased excretion of porphyrin and porphyrin precursor had normal activity of erythrocyte porphobilinogen deaminase (EC 4.3.1.8) and leukocyte protoporphyrinogen oxidase (EC 1.3.3.4). Clinical symptoms, coincident with the excretion of rose-colored urine, were consistent with the diagnosis of an acute porphyria. The disease resolved spontaneously after the withdrawal of carbamazepine and sodium valproate and the commencement of parenteral nutrition with subsequent carbohydrate loading. In addition to normal concentrations of enzyme activities, the patient is unusual in presenting before puberty and in having no family history of porphyria.

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