scholarly journals ABCB6 Polymorphisms are not Overly Represented in Patients with Porphyria

2021 ◽  
Author(s):  
Colin P Farrell ◽  
Gaël Nicolas ◽  
Robert J. Desnick ◽  
Charles J. Parker ◽  
Jerome Lamoril ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Acute Intermittent Porphyria ◽  
Mendelian Inheritance ◽  
Erythropoietic Protoporphyria ◽  
Transporter Protein ◽  
Hereditary Coproporphyria ◽  
Knockout Animals

The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.

scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

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.

Amounts of Faecal Porphyrin-Peptide Conjugates in the Porphyrias

1972 ◽  
Vol 43 (2) ◽  
pp. 299-302 ◽  
Author(s):  
M. R. Moore ◽  
G. G. Thompson ◽  
A. Goldberg
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Acute Intermittent Porphyria ◽  
Normal Subjects ◽  
Erythropoietic Protoporphyria ◽  
Peptide Conjugates ◽  
Peptide Complex ◽  
Variegate Porphyria ◽  
Hereditary Coproporphyria ◽  
Different Types

1. The levels of ‘X-porphyrin’, a porphyrin-peptide complex, have been studied in the faeces of patients with different types of porphyria, as well as in fifty normal subjects. 2. These levels have been shown to be significantly elevated in untreated porphyria cutanea tarda and in variegate porphyria. 3. Lesser elevations were seen in acute intermittent porphyria and hereditary coproporphyria. There was no elevation in erythropoietic protoporphyria.

The Porphyrias

2016 ◽  
Author(s):  
Karl E Anderson ◽  
Attallah Kappas
Keyword(s):  
Biosynthetic Pathway ◽  
Aminolevulinic Acid ◽  
Clinical Symptoms ◽  
Porphyria Cutanea Tarda ◽  
Acute Intermittent Porphyria ◽  
Genetic Traits ◽  
Molecular Defects ◽  
Clinical Presentations ◽  
Congenital Erythropoietic Porphyria ◽  
Hereditary Coproporphyria

The porphyrias are uncommon disorders caused by deficiencies in the activities of enzymes of the heme biosynthetic pathway. The enzymatic defects that cause porphyrias are inherited, with the exception of porphyria cutanea tarda, which is primarily acquired. In all porphyrias, there is significant interplay between genetic traits and acquired or environmental factors in the expression of clinical symptoms. This review discusses the classification, pathophysiology, and clinical presentations of the porphyrias. These include those associated with neurovisceral attacks (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase [alad] deficiency porphyria) and the porphyrias associated with cutaneous photosensitivity (porphyria cutanea tarda, hepatoerythropoietic porphyria, erythropoietic protoporphyria, and congenital erythropoietic porphyria). Specific emphasis on the epidemiology, molecular defects and pathophysiology, clinical features, diagnosis, and treatment are discussed for each of these disorders. A table lists the safe and unsafe drugs for patients with porphyrias. Figures illustrate the genetic pathways of the disorders and the activities of enzymes of the heme biosynthetic pathway. This review contains 2 highly rendered figures, 1 table, and 96 references.

scholarly journals Plasma Porphyrins in the Porphyrias

1999 ◽  
Vol 45 (7) ◽  
pp. 1070-1076 ◽  
Author(s):  
J Thomas Hindmarsh ◽  
Linda Oliveras ◽  
Donald C Greenway
Keyword(s):  
Renal Failure ◽  
Healthy Subjects ◽  
Porphyria Cutanea Tarda ◽  
Plasma Concentrations ◽  
Acute Intermittent Porphyria ◽  
Fluorometric Detection ◽  
Erythropoietic Protoporphyria ◽  
Clinical Sensitivity ◽  
Hereditary Coproporphyria ◽  
Coproporphyrin I

Abstract Background: As an aid in the diagnosis and management of porphyria we have developed a method to fractionate and quantify plasma porphyrins and have evaluated its use in various porphyrias. Methods: We used HPLC with fluorometric detection to measure plasma concentrations of uroporphyrin I and III, heptacarboxyl III, hexacarboxyl III, pentacarboxyl III, and coproporphyrin I and III. We studied 245 healthy subjects, 32 patients with classical porphyria cutanea tarda (PCT), 12 patients with PCT of renal failure, 13 patients with renal failure, 8 patients with pseudoporphyria of renal failure, 3 patients with acute intermittent porphyria, 5 patients with variegate porphyria, 5 patients with hereditary coproporphyria, and 4 patients with erythropoietic protoporphyria. Results: Between-run CVs were 5.4–13%. The recoveries of porphyrins added to plasma were 71–114% except for protoporphyrin, which could not be reliably measured with this technique. Plasma porphyrin patterns clearly identified PCT, and its clinical sensitivity equaled that of urine porphyrin fractionation. The patterns also allowed differentiation of PCT of renal failure from pseudoporphyria of renal failure. Conclusions: The assay of plasma porphyrins identifies patients with PCT and appears particularly useful for differentiating PCT of renal failure from pseudoporphyria of renal failure.

The FHM1 Mutation S218L: A Severe Clinical Phenotype? A Case Report and Review of the Literature

Cephalalgia ◽  
2009 ◽  
Vol 29 (12) ◽  
pp. 1337-1339 ◽  
Author(s):  
S Debiais ◽  
C Hommet ◽  
I Bonnaud ◽  
MA Barthez ◽  
S Rimbaux ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Cerebral Oedema ◽  
Clinical Phenotype ◽  
Pregnant Patient ◽  
Familial Hemiplegic Migraine ◽  
Review Of The Literature ◽  
Severe Phenotype ◽  
Hemiplegic Migraine ◽  
Motor Weakness ◽  
Cacna1a Gene

Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of migraine with aura that is characterized by motor weakness during attacks. FHM1 is associated with mutations in the CACNA1A gene located on chromosome 19. We report a severe, prolonged HM attack in a young pregnant patient who had the S218L FHM1. This CACNA1A mutation has been associated with HM, delayed cerebral oedema and coma following minor head trauma. The case history we report suggests a specific, severe phenotype and the co-occurrence of HM and epilepsy related to the S218L FHM1 mutation.

When sleep-related hypermotor epilepsy (SHE) met Charles Darwin and Francis Galton

Neurology ◽  
2017 ◽  
Vol 89 (5) ◽  
pp. 502-505 ◽  
Author(s):  
Liborio Parrino ◽  
Giovanni Pavesi
Keyword(s):  
Differential Diagnosis ◽  
Genetic Factors ◽  
Charles Darwin ◽  
Autosomal Dominant ◽  
Behavior Disorder ◽  
Rem Behavior Disorder ◽  
Genetic Transmission ◽  
Francis Galton ◽  
Expression Of Emotions ◽  
Autosomal Inheritance

Sleep-related hypermotor epilepsy (SHE) is characterized by short-lasting seizures patterned by repetitive and stereotyped motor events in the same person. In autosomal dominant SHE, genetic factors play a well-known key role. In The Expression of Emotions in Man and Animals, Charles Darwin quotes a plausible example of SHE illustrated by his cousin Sir Francis Galton: “the gentleman…lay fast asleep on his back in bed, raising his right arm slowly in front of his face, up to his forehead, and then dropping it with a jerk, so that the wrist fell heavily on the bridge of his nose. The trick did not occur every night, but occasionally, and was independent of any ascertained cause. Sometimes it was repeated incessantly for an hour or more.” Similar manifestations during sleep occurred also in the patient's son and granddaughter, suggesting an autosomal inheritance without sex relationship. Differential diagnosis with REM behavior disorder and other parasomnias is discussed. To our knowledge, this could be the first description of a stereotyped SHE pattern with genetic transmission.

scholarly journals Rapid Quantitative Method Using Spin Columns to Measure Porphobilinogen in Urine

2008 ◽  
Vol 54 (2) ◽  
pp. 429-431 ◽  
Author(s):  
Mikhail Roshal ◽  
Jeanne Turgeon ◽  
Petrie M Rainey
Keyword(s):  
Quantitative Method ◽  
Quantitative Methods ◽  
Exchange Resin ◽  
Anion Exchange Resin ◽  
Acute Intermittent Porphyria ◽  
Acute Porphyria ◽  
Spin Column ◽  
Deming Regression ◽  
Hereditary Coproporphyria ◽  
Urine Specimens

Abstract Background: Large increases of urinary porphobilinogen (PBG) indicate acute porphyria, which may be due to acute intermittent porphyria, variegate porphyria, or hereditary coproporphyria. These conditions are relatively rare but share symptoms with more common conditions, such as acute surgical abdomen, and often must be ruled out rapidly. Reported quantitative methods for PBG measurement are time-consuming and inconvenient. We developed a rapid quantitative method that uses resin-packed spin columns to measure PBG in urine. Method: We applied urine to anion exchange resin in a spin column, then performed centrifugal separation and washing. PBG was eluted in 1 mol/L acetic acid and reacted with Ehrlich’s reagent. After 5 min, we measured absorbance at 525, 555, and 585 nm. PBG concentration (mg/L) was calculated as 88 (A555 − ½(A525 + A585)). Results: The reportable PBG concentration range was 0.2–15 mg/L. Between-day (total) imprecision (CV) was 8.4% at 1.2 mg/L and 3.5% at 4.4 mg/L. Comparison with our established method (x) yielded a Deming regression equation: y = 1.04x − 0.01 mg/L (R2 = 0.98; Sy,x = 0.87 mg/L). No interference was noted from urobilinogen or highly colored urine specimens. Conclusions: This method for PBG measurement is more rapid and precise than other methods. This test can serve as a quick screening test and facilitates batch analysis for routine quantitative testing.

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