scholarly journals DOUBLE PORPHYRIA: LITERATURE REVIEW AND ANALYSIS OF CLINICAL OBSERVATION

2018 ◽  
Vol 21 (2) ◽  
pp. 120-124
Author(s):  
Alexander B. Krivosheev ◽  
L. Ya Kupriyanova ◽  
M. A Kondratova
Keyword(s):  
Aminolevulinic Acid ◽  
Clinical Symptoms ◽  
Dorsal Surface ◽  
Total Content ◽  
Acute Intermittent Porphyria ◽  
Aminocaproic Acid ◽  
Progressive Increase ◽  
New Variant ◽  
Peripheral Polyneuropathy ◽  
Prolonged Observation

A brief review of the literature on the problem of double porphyria and analysis of its own observation is presented. For more than 10 years patient B was observed for more than 10 years with a verified diagnosis of acute intermittent porphyria, which manifested with acute pain abdominal syndrome, neurological disorders in the form of peripheral polyneuropathy and hemiparesis of lower extremities, and hypertension syndrome was also noted. The observed clinical symptoms corresponded to an acute porphyrin crisis in the manifestation and / or relapse of acute intermittent porphyria. The diagnosis was confirmed by a quantitative determination of the excretory profile of porphyrin precursors (δ-aminocaproic acid, porphobilinogen) and porphyrin fractions (uroporphyrin, coproporphyrin). Their concentrations are significantly (especially porphyrin precursors) exceeding the control values, which is the cardinal diagnostic criterion of acute intermittent porphyria. Against the backdrop of persistent clinical and biochemical remission of acute intermittent porphyria, symptoms of photosensitization of the skin (blisters, erosion, pigment spots) on the dorsal surface of the hands began to appear in 4 years. Later, hypertrichosis was formed in the temporo-periorbital region. The constellation type of the excretory profile of porphyrins began to change. Against the backdrop of persistent increased excretion of porphyrin precursors (δ-aminolevulinic acid and porphobilinogen), a progressive increase in the excretion of the fraction of uroporphyrin was observed, which became dominant (up to 58% of the total content of porphyrins). Such a prolonged observation in the dynamics allowed us to state the appearance of a new variant of the porphyrin exchange disturbance, which, taking into account clinical symptoms, corresponded to another form of hepatic porphyria, namely, late cutaneous porphyria. The clinical and biochemical changes in the excretory profile of the parameters of porphyrin metabolism registered in the dynamics of observation may indicate the occurrence of a combined enzymatic defect characteristic of double porphyria. In our case, a manifestation of late cutaneous porphyria was noted against a background of compensated acute intermittent porphyria.

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 Predictive Outcome Modeling of Preoperative Clinical Symptoms and Electrodiagnostic Data in Tarsal Tunnel Surgery

2021 ◽  
Vol 16 (01) ◽  
pp. e37-e45
Author(s):  
Geoffrey K. Seidel ◽  
Salma Al Jamal ◽  
Eric Weidert ◽  
Frederick Carington ◽  
Michael T. Andary ◽  
...  
Keyword(s):  
Surgical Outcome ◽  
Clinical Symptoms ◽  
Tibial Nerve ◽  
Outcome Measurement ◽  
Tarsal Tunnel ◽  
Patient Reported ◽  
Peripheral Polyneuropathy ◽  
Tunnel Syndrome ◽  
Phalen's Test ◽  
Surgical Release

Abstract Background The relationship between tarsal tunnel syndrome (TTS), electrodiagnostic (Edx) findings, and surgical outcome is unknown. Analysis of TTS surgical release outcome patient satisfaction and comparison to Edx nerve conduction studies (NCSs) is important to improve outcome prediction when deciding who would benefit from TTS release. Methods Retrospective study of 90 patients over 7 years that had tarsal tunnel (TT) release surgery with outcome rating and preoperative tibial NCS. Overall, 64 patients met study inclusion criteria with enough NCS data to be classified into one of the following three groups: (1) probable TTS, (2) peripheral polyneuropathy, or (3) normal. Most patients had preoperative clinical provocative testing including diagnostic tibial nerve injection, tibial Phalen's sign, and/or Tinel's sign and complaints of plantar tibial neuropathic symptoms. Outcome measure was percentage of patient improvement report at surgical follow-up visit. Results Patient-reported improvement was 92% in the probable TTS group (n = 41) and 77% of the non-TTS group (n = 23). Multivariate modeling revealed that three out of eight variables predicted improvement from surgical release, NCS consistent with TTS (p = 0.04), neuropathic symptoms (p = 0.045), and absent Phalen's test (p = 0.001). The R 2 was 0.21 which is a robust result for this outcome measurement process. Conclusion The best predictors of improvement in patients with TTS release were found in patients that had preoperative Edx evidence of tibial neuropathy in the TT and tibial nerve plantar symptoms. Determining what factors predict surgical outcome will require prospective evaluation and evaluation of patients with other nonsurgical modalities.

scholarly journals FGF23, a novel muscle biomarker detected in the early stages of ALS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Si ◽  
Mohamed Kazamel ◽  
Michael Benatar ◽  
Joanne Wuu ◽  
Yuri Kwon ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Fold Increase ◽  
Progressive Increase ◽  
Molecular Signature ◽  
Muscle Membrane ◽  
Sequencing Project ◽  
Progressive Muscle Weakness ◽  
End Stage

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

scholarly journals Biochemical and hematological analysis in acute intermittent porphyria (AIP): a case report

2013 ◽  
Vol 85 (3) ◽  
pp. 1207-1214 ◽  
Author(s):  
ANNA R.R. DOS SANTOS ◽  
RAFAELA R. DE ALBUQUERQUE ◽  
MARIA J.R. DORIQUI ◽  
GRACIOMAR C. COSTA ◽  
ANA PAULA S.A. DOS SANTOS
Keyword(s):  
Biochemical Parameters ◽  
Contraceptive Use ◽  
Aminolevulinic Acid ◽  
Neuropsychiatric Symptoms ◽  
Acute Intermittent Porphyria ◽  
Signs And Symptoms ◽  
Acute Porphyria ◽  
Reactive Protein ◽  
Hematological Analysis ◽  
Hematological And Biochemical Parameters

Acute intermittent porphyria is the most common acute porphyria caused by a decrease in hepatic porphobilinogen deaminase activity, resulting in an accumulation of delta-aminolevulinic acid and porphobilinogen. This disease shows nonspecific signs and symptoms that can be confused with other diseases, thereby making the diagnosis difficult. We report a case of acute intermittent porphyria, reviewing clinical and laboratory aspects, highlighting the hematological and biochemical parameters during and after the crisis. A female patient, aged 28 years, suffered two crises, both presenting gastrointestinal disorders. The second presented neuropsychiatric symptoms. The analysis of hematological and biochemical parameters during the second crisis showed anemia, leukocytosis, hyponatremia, mild hypokalemia, uremia and elevated C-reactive protein. The initial treatment included glucose infusion, a diet rich in carbohydrates and interruption of porphyrinogenic drugs. Subsequently, treatment was maintained with oral contraceptive use. According to the observed data, signs and symptoms of gastrointestinal, neurological and psychiatric disorders, associated with laboratory results presented in this paper can be applied to screen acute porphyria, contributing to early diagnosis.

scholarly journals Placental markers of folate-related metabolism in preeclampsia

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 467-476 ◽  
Author(s):  
C Mislanova ◽  
O Martsenyuk ◽  
B Huppertz ◽  
M Obolenskaya
Keyword(s):  
Clinical Symptoms ◽  
Total Content ◽  
Plasma Homocysteine ◽  
Positive Relation ◽  
Rt Pcr ◽  
Methylene Tetrahydrofolate Reductase ◽  
Tight Association ◽  
The Impact ◽  
First Time ◽  
Related Compounds

The etiology and degree of clinical symptoms of preeclampsia depend on genotypic and phenotypic maternal and trophoblast factors, and elevated levels of plasma homocysteine (Hcy) are one of the pathogenetic factors of preeclampsia. To assess the impact of the folate-related metabolism, we characterized the indices of this metabolism in 40 samples from uncomplicated term placentas and 28 samples from preeclamptic pregnancies by quantifying the total content of folate, methionine (Met), Hcy and related cysteine, and glutathione (GSH) in compliance with the 677 C/T genotype of methylene tetrahydrofolate reductase (MTHFR). The prevalence ofMTHFRgenotypes was not significantly different between the two groups. The polymorphism ofMTHFRwas not unambiguously connected with the content of total placental Met, Hcy and related cysteine, and GSH either in uncomplicated or in complicated pregnancies. By contrast, the combination of the heterozygousMTHFRgenotype with folate deficiency in the samples from preeclamptic pregnancies was characterized by a statistically significant decrease in the Met content, a trend toward increased Hcy levels and a tight association between metabolically directly and indirectly related compounds, e.g. positive relation between Hcy versus cysteine and folate versus GSH and negative relation between folate versus Hcy and both Hcy and cysteine versus GSH. We demonstrated the expression of cystathionine-β-synthase (CBS) in human placenta at term by RT-PCR and western blot analysis, for the first time, and confirmed its catalytic activity and the accumulation of cysteine and CBS in placental explants cultivated in the presence of elevated Hcy concentrations. We suggest that disturbance in placental folate-related metabolism may be one of the pathogenetic factors in preeclampsia.

Transthyretin-assoziierte familiäre Amyloidpolyneuropathie

2018 ◽  
Vol 143 (06) ◽  
pp. 427-430
Author(s):  
Christoph Niemietz ◽  
Christoph Röcken ◽  
Matthias Schilling ◽  
Jörg Stypman ◽  
Constantin Uhlig ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Clinical Symptoms ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Correct Diagnosis ◽  
Vitreous Body ◽  
Final Diagnosis ◽  
Autonomic Nerves ◽  
Loss Of Weight ◽  
Peripheral Polyneuropathy ◽  
Immunohistochemical Evidence

AbstractTransthyretin-related Familial Amyloid Polyneuropathy (ATTR Amyloidosis, former FAP, here called TTR-FAP) is a rare, progressive autosomal dominant inherited amyloid disease ending fatal within 5 – 15 years after final diagnosis. TTR-FAP is caused by mutations of transthyretin (TTR), which forms amyloid fibrils affecting peripheral and autonomic nerves, the heart and other organs. Due to the phenotypic heterogeneity and partly not specific enough clinical symptoms, diagnosis of TTR-FAP can be complicated. False diagnoses can include idiopathic polyneuropathy, chronic inflammatory demyelinating polyneuropathy, diabetic neuropathy as well as paraneoplastic syndrome. Hence, it is assumed that many cases remain unreported. Early and correct diagnosis of TTR-FAP is crucial, since appropriate therapeutic options exist. TTR-FAP should always be differentially diagnosed, when apart from a progressive peripheral polyneuropathy, additional symptoms as autonomic dysfunction, cardiomyopathy, gastrointestinal disorders, unexpected loss of weight, carpal tunnel syndrome, restrictions of renal function, epileptic fits, and corneal and vitreous body clouding occur. Histological evidence of amyloid and successive immunohistochemical evidence of transthyretin as well as genetic testing for transthyretin mutations, lead to an accurate diagnosis.

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.

scholarly journals Correlation between plasma 5-aminolevulinic acid concentrations and indicators of oxidative stress in lead-exposed workers

1997 ◽  
Vol 43 (7) ◽  
pp. 1196-1202 ◽  
Author(s):  
Cristine A Costa ◽  
Gilmar C Trivelato ◽  
Adriana M P Pinto ◽  
Etelvino J H Bechara
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Lead Poisoning ◽  
Stress Responses ◽  
Aminolevulinic Acid ◽  
Aerobic Oxidation ◽  
Protoporphyrin Ix ◽  
Acute Intermittent Porphyria ◽  
Blood Concentrations ◽  
Exposed Workers

Abstract 5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria and lead poisoning, undergoes metal-catalyzed aerobic oxidation at physiological pH to yield reactive free radical species (O2−·>, HO·, and ALA·). We analyzed the relationships between plasma ALA concentrations, blood concentrations of lead, protoporphyrin IX (PP-IX), superoxide dismutase (SOD), and methemoglobin (metHb), and urine chemiluminescence (CL) in samples collected from lead-exposed workers. All variables measured were substantially (P <0.01) higher (2–8-fold) in the lead-exposed workers (n = 60). Plasma ALA concentrations were, on average, 6-fold higher in lead-exposed workers. We observed positive linear relationships between ALA and lead (r = 0.992), ALA and PP-IX (r = 0.891), ALA and metHb (r = 0.984), lead and SOD (r = 0.948), ALA and urine CL (r = 0.987), and lead and PP-IX (r = 0.993). These data are consistent with our free radical hypothesis for lead poisoning, where ALA distribution to and accumulation in several organs may trigger oxidative stress responses.

scholarly journals A Red Cell Enzyme Method for the Diagnosis of Acute Intermittent Porphyria

Blood ◽  
1974 ◽  
Vol 44 (6) ◽  
pp. 857-868 ◽  
Author(s):  
C. Richard Magnussen ◽  
Joel B. Levine ◽  
Joyce M. Doherty ◽  
Judy O. Cheesman ◽  
Donald P. Tschudy
Keyword(s):  
Aminolevulinic Acid ◽  
Acute Intermittent Porphyria ◽  
Mean Value ◽  
Red Cells ◽  
Red Cell ◽  
Enzyme Preparations ◽  
Cell Enzyme ◽  
Enzyme Method ◽  
Latent Disease ◽  
The Mean

Abstract A method has been devised for the measurement of uroporphyrinogen I synthetase ih red cells. By using trichloroacetic acid as a protein precipitant, heme is removed from the final solution, allowing accurate measurement of porphyrins. The method is highly reproducible and adaptable to varying incubation volumes and enzyme preparations. It is of great value as an enzyme diagnostic method for acute intermittent porphyria and appears capable of detecting patients with the latent disease who have normal urinary δ-aminolevulinic acid and porphobilinogen excretion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. The mean value of the enzyme in red cells of patients with acute intermittent porphyria was approximately 50% that of normals, indicating that the mutation causes complete lack of catalytic activity in the mutant enzyme.

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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