Acute intermittent porphyria caused by a C?T mutation that produces a stop codon in the porphobilinogen deaminase gene

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.

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Mild Encephalitis/Encephalopathy with Reversible Splenial Lesion (MERS) due to Acute Intermittent Porphyria with a novel mutation in the porphobinoglien deaminase gene

10.21203/rs.2.19929/v1 ◽

2020 ◽

Author(s):

xiaoqing li ◽

fei han ◽

qianlong chen ◽

tienan zhu ◽

yongqiang zhao ◽

...

Keyword(s):

Autosomal Dominant ◽

Stop Codon ◽

Novel Mutation ◽

Acute Intermittent Porphyria ◽

Porphobilinogen Deaminase ◽

Splicing Mutation ◽

Autosomal Dominant Disorder ◽

The Third ◽

Splenial Lesion ◽

Partial Deficiency

Abstract Background: Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by a reversible isolated lesion with transiently reduced diffusion in the central portion of the splenium of the corpus callosum (SCC). The reason for MERS is unknown. however, infectious-related MERS (in particular virus) 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 of hemebiosynthetic 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 MR manifestations suggestive of MERS, she had a novel PBGD splicing mutation, a G to A mutation in base 594 resulting in tryptophan to a stop codon (W198*). Conclusion: To the best of our knowledge, this is only one published case of MERS associated with AIP.

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Recurrence risk estimation of acute intermittent porphyria based on analysis of porphobilinogen deaminase activity: A Bayesian approach

American Journal of Medical Genetics ◽

10.1002/ajmg.1320190415 ◽

1984 ◽

Vol 19 (4) ◽

pp. 755-762 ◽

Cited By ~ 17

Author(s):

C. Bonaïti-Pellié ◽

L. Phung ◽

Y. Nordmann

Keyword(s):

Bayesian Approach ◽

Risk Estimation ◽

Acute Intermittent Porphyria ◽

Recurrence Risk ◽

Porphobilinogen Deaminase

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Prophylactic Heme Arginate Infusion for Acute Intermittent Porphyria

Frontiers in Pharmacology ◽

10.3389/fphar.2021.712305 ◽

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.

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

Molecular Medicine ◽

10.1007/bf03401859 ◽

2001 ◽

Vol 7 (8) ◽

pp. 535-542 ◽

Cited By ~ 21

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

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Safety, Pharmacokinetics and Pharmocodynamics of Recombinant Human Porphobilinogen Deaminase in Healthy Subjects and Asymptomatic Carriers of the Acute Intermittent Porphyria Gene Who Have Increased Porphyrin Precursor Excretion

Clinical Pharmacokinetics ◽

10.2165/00003088-200746040-00006 ◽

2007 ◽

Vol 46 (4) ◽

pp. 335-349 ◽

Cited By ~ 23

Author(s):

Eliane Sardh ◽

Lillan Rejkj??r ◽

Dan E H Andersson ◽

Pauline Harper

Keyword(s):

Healthy Subjects ◽

Acute Intermittent Porphyria ◽

Porphobilinogen Deaminase ◽

Asymptomatic Carriers

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Variant acute intermittent porphyria in a child

Clinical Chemistry ◽

10.1093/clinchem/36.5.812 ◽

1990 ◽

Vol 36 (5) ◽

pp. 812-814 ◽

Cited By ~ 2

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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