56 results match your criteria: "ALA Dehydratase Deficiency Porphyria"
Profound hypotonia in an infant with δ-aminolevulinic acid dehydratase deficient porphyria.
Eur J Hum Genet
December 2024
Department of Neonatology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
δ-Aminolevulinic acid (ALA) dehydratase (ALAD) deficient porphyria (ADP) is an extremely rare form of porphyria, with only eight documented cases. Herein, we report the second known case of ADP in the Western hemisphere and third case with infantile onset of symptoms. A male neonate presented on day three of life with profound hypotonia, pinpoint pupils, absent deep tendon reflexes, and anemia.
View Article and Find Full Text PDFTherapeutic approach to acute crises of hepatic porphyrias.
Rev Clin Esp (Barc)
December 2024
Unidad de Enfermedades Raras y Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Article Synopsis
- - Acute hepatic porphyria is a genetic disorder that affects the production of heme and is primarily caused by issues with specific enzymes, with acute intermittent porphyria being the most common type.
- - Triggered by factors that induce the enzyme ALA synthase 1, this disorder leads to the buildup of toxic heme intermediates, causing severe symptoms such as abdominal pain, muscle weakness, and autonomic dysfunction; women are more prone to these attacks than men.
- - Prompt recognition and treatment are essential, requiring urgent medical interventions like intravenous opioids and glucose, while preventive measures include hormone suppression and possibly liver transplantation.
Quantification of Urine and Plasma Porphyrin Precursors Using LC-MS in Acute Hepatic Porphyrias: Improvement in Routine Diagnosis and in the Monitoring of Kidney Failure Patients.
Clin Chem
October 2023
Université de Paris Cité, INSERM U1149, Centre de Recherche sur l'Inflammation, HIROS Team, F-75018 Paris, France.
Background: The quantification of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine are the first-line tests for diagnosis and monitoring of acute hepatic porphyrias (AHP). Ion-exchange chromatography (IEC), which is time- and staff-consuming and limited to urine, is still the preferred method in many specialized laboratories, despite the development of mass spectrometry-based methods.
Methods: We describe a new LC-MS method that allows for rapid and simple quantification of ALA and PBG in urine and plasma with an affordable instrument that was used to analyze 2260 urine samples and 309 blood samples collected in 2 years of routine activity.
RNA interference therapy in acute hepatic porphyrias.
Blood
November 2023
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
The acute hepatic porphyrias (AHPs) are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks precipitated by factors that upregulate hepatic 5-aminolevulinic acid synthase 1 (ALAS1) activity. Induction of hepatic ALAS1 leads to the accumulation of porphyrin precursors, in particular 5-aminolevulinic acid (ALA), which is thought to be the neurotoxic mediator leading to acute attack symptoms such as severe abdominal pain and autonomic dysfunction. Patients may also develop debilitating chronic symptoms and long-term medical complications, including kidney disease and an increased risk of hepatocellular carcinoma.
View Article and Find Full Text PDFPharmacokinetic-pharmacodynamic model of urinary δ-aminolevulinic acid reduction after givosiran treatment in patients with acute hepatic porphyria.
CPT Pharmacometrics Syst Pharmacol
June 2023
Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA.
Givosiran, an RNA interference-based therapeutic, is a recent addition to the limited treatment armamentarium for acute hepatic porphyria (AHP). As a small interfering RNA that is selectively taken up in the liver, both the mechanism and targeted delivery create a complex relationship between givosiran pharmacokinetics (PK) and the pharmacodynamic (PD) response. Using pooled data from phase I-III clinical trials of givosiran, we developed a semimechanistic PK/PD model to describe the relationship between predicted liver and RNA-induced silencing complex concentrations of givosiran and the associated reduction in synthesis of δ-aminolevulinic acid (ALA), a toxic heme intermediate that accumulates in patients with AHP, contributing to disease pathogenesis.
View Article and Find Full Text PDFPrevalence of Undiagnosed Acute Hepatic Porphyria in Cyclic Vomiting Syndrome and Overlap in Clinical Symptoms.
Dig Dis Sci
May 2023
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University College of Medicine, 395 W 12th Avenue, Columbus, OH, 43210, USA.
Background And Aims: Acute hepatic porphyria (AHP) presents with nausea and vomiting and can mimic cyclic vomiting syndrome (CVS). The prevalence of AHP in CVS and overlap in clinical symptomatology is not known. We thus sought to determine the prevalence of pathogenic variants for AHP and characterize symptom overlap between CVS and AHP.
View Article and Find Full Text PDFDisease burden in patients with acute hepatic porphyria: experience from the phase 3 ENVISION study.
Orphanet J Rare Dis
August 2022
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Article Synopsis
- Acute hepatic porphyria (AHP) includes four rare genetic disorders that cause a buildup of neurotoxic substances, leading to severe neurological symptoms and complications.
- In a trial of givosiran, an RNA-based treatment, researchers examined patients aged 12+ to evaluate the drug's effectiveness in reducing the frequency and severity of debilitating attacks compared to a placebo.
- Results showed that patients with AHP experienced significant chronic symptoms and poor quality of life, but givosiran effectively reduced attack frequency, pain severity, and reliance on opioid medications.
Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria.
Front Genet
August 2022
Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL, United States.
5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an autosomal recessive disease characterized by a profound deficiency in ALAD, the second enzyme in the heme biosynthetic pathway, and acute neurovisceral attacks with abdominal pain and peripheral neuropathy. Hemin infusions are often effective in treating and preventing such attacks. Givosiran was recently approved for prevention of attacks of acute hepatic porphyrias (AHPs), including ADP, but, to our knowledge, has not yet been applied in patients with this ultrarare disease.
View Article and Find Full Text PDFSpotlight on Givosiran as a Treatment Option for Adults with Acute Hepatic Porphyria: Design, Development, and Place in Therapy.
Drug Des Devel Ther
June 2022
Department of Internal Medicine, Section on Gastroenterology and Hepatology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Article Synopsis
- Small interfering RNAs (siRNAs) are tiny RNA pieces that can make messenger RNA (mRNA) disappear, which helps control how much protein is made in our bodies.
- Givosiran is a special siRNA that helps treat a rare liver disease called acute hepatic porphyrias by targeting a specific part of the liver that creates toxic substances.
- The text talks about how givosiran works, its successful test results, and its importance for treating this disease and potentially helping with other medical problems in the future.
Neurological Manifestations of Acute Porphyrias.
Curr Neurol Neurosci Rep
July 2022
Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, 912 S Wood St, Chicago, IL, 60612, USA.
Article Synopsis
- Porphyrias are rare disorders caused by a lack in the heme biosynthetic pathway, leading to the buildup of certain metabolic intermediates, which can cause severe symptoms in patients.
- The condition can present with a range of issues including severe abdominal pain, gastrointestinal symptoms, skin sensitivity, and various neurologic problems such as altered consciousness and seizures.
- Recent findings suggest that neurologic issues linked to porphyria may be more common and severe than previously recognized, including conditions like posterior reversible encephalopathy syndrome, emphasizing the need for further understanding and treatment strategies.
Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence-based screening assay.
Pharmacol Res Perspect
June 2022
Department of Internal Medicine, Section on Gastroenterology and Hepatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Article Synopsis
- Compounds that induce 5-aminolevulinic acid synthase-1 or cytochromes P-450 can trigger acute porphyric attacks in patients with acute hepatic porphyrias, but there's currently no reliable model to predict which drugs can do this.
- Researchers developed a fluorescence-based in vitro assay using various liver cell culture models to assess the porphyrogenicity of selected compounds, measuring fluorescence from protoporphyrin IX, an important heme biosynthesis intermediate.
- Among the different cell cultures tested, LMH cells showed the highest fluorescence and therefore were concluded to be an effective and cost-efficient system to predict which compounds might exacerbate acute hepatic porphyrias.
RNAi therapy with givosiran significantly reduces attack rates in acute intermittent porphyria.
J Intern Med
May 2022
Department of Medical Biochemistry and Biophysics, Centre for inherited Metabolic Diseases, Porphyria Centre Sweden., Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Article Synopsis
- Acute hepatic porphyria (AHP) is a genetic disorder affecting heme production, leading to dangerous neurovisceral attacks that significantly impair quality of life.
- The traditional treatment was hemin infusion, and liver transplantation was the only cure, but new therapies are emerging based on molecular engineering to target the heme synthesis pathway.
- Givosiran, an approved drug for patients aged 12 and older, has shown in clinical trials to effectively reduce markers associated with AHP and decrease the frequency of acute attacks compared to a placebo.
Acute porphyrias - A neurological perspective.
Brain Behav
November 2021
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology, Berlin, Germany.
Article Synopsis
- Acute hepatic porphyrias (AHP) are rare genetic disorders that lead to severe neurological symptoms due to deficiencies in enzymes involved in heme production, with four main types identified.
- Diagnosis is often delayed or mistaken because of their varying presentations and similarities to conditions like Guillain-Barré syndrome and autoimmune encephalitis.
- Key indicators for suspecting AHP include neurological symptoms appearing after severe abdominal pain, reddish urine, hyponatremia, photodermatitis, and signs of encephalopathy or neuropathy, as illustrated by three case studies from a neurological intensive care unit.
Expert consensus statement on acute hepatic porphyria in Belgium.
Acta Clin Belg
August 2022
Dienst Maag-Darm-Leverziekten en Metabool Centrum, UZ Leuven, Belgium.
Article Synopsis
- Acute hepatic porphyrias (AHP) are rare and serious diseases that can cause a lot of problems for around 11-34 patients in Belgium who need help.
- Currently, there are no effective medications to prevent attacks or help with the ongoing symptoms these patients suffer from.
- Experts from two important medical centers in Belgium and a pharmaceutical company met to discuss AHP and created a guideline to better understand and care for patients with these diseases.
5-Aminolevulinate dehydratase porphyria: Update on hepatic 5-aminolevulinic acid synthase induction and long-term response to hemin.
Mol Genet Metab
December 2020
Departments of Preventive Medicine and Population Health, and Internal Medicine (Division of Gastroenterology and Hepatology), University of Texas Medical Branch, Galveston, Texas, USA.
Article Synopsis
- 5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an extremely rare autosomal recessive condition with only eight cases documented, all in males, and is poorly understood due to limited follow-up and treatment data.
- The sixth reported ADP patient, a 31-year-old male from the Americas, showed elevated mRNA for the enzyme 5-aminolevulinic acid synthase-1 (ALAS1), but did not have the modifying mutation found in other porphyrias.
- Treatment with intravenous hemin has been effective in most cases, highlighting the liver's key role in the production of excess 5-aminolevulinic acid (ALA
Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad?
Eur J Intern Med
September 2020
Unit of Internal Medicine, Department of Medical and Surgical Science for Children and Adults, University of Modena and Reggio Emilia, Italy.
Article Synopsis
- Acute porphyrias (AP) are linked to heme deficiency and elevated levels of homocysteine (Hcy), which can harm blood vessels and lead to various health issues.
- A study of 46 AP patients revealed that those showing symptoms had significantly higher levels of urinary biomarkers (ALA and PBG), plasma Hcy, and a higher prevalence of hyperhomocysteinemia (HHcy) compared to asymptomatic patients.
- The findings suggest that the presence of HHcy in symptomatic AP patients may indicate issues with sulfur amino acid metabolism and potentially connect to the disease's pathogenesis and related health problems.
Heme biosynthesis and the porphyrias.
Mol Genet Metab
November 2019
Division of Hematology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States of America. Electronic address:
Article Synopsis
- Porphyrias are a group of genetic metabolic disorders characterized by defective enzymes in the heme biosynthetic pathway, resulting in the accumulation of specific intermediates.
- Symptoms vary by type, leading to either neurological issues or skin reactions (photocutaneous symptoms), and diagnosis is based on the patterns of these intermediates in body fluids.
- Porphyrias can be classified as either erythropoietic (like congenital erythropoietic porphyria) or hepatic (like acute intermittent porphyria), with eight specific enzymes linked to distinct types of the disease.
Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs).
Mol Genet Metab
November 2019
Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine/NC Baptist Hospital, Winston-Salem, NC 27157, United States of America.
The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes.
View Article and Find Full Text PDFAcute Hepatic Porphyrias: Review and Recent Progress.
Hepatol Commun
February 2019
Section of Gastroenterology and Hepatology, Department of Internal Medicine Wake Forest University School of Medicine Winston-Salem NC.
Article Synopsis
- The acute hepatic porphyrias (AHPs) are four inherited disorders affecting heme production, causing severe neurovisceral symptoms that often resemble other illnesses, leading to misdiagnosis.
- Acute intermittent porphyria is the most common and severe type, with a higher prevalence than previously known, particularly affecting women aged 14-45.
- Current treatment involves urgent intravenous heme therapy for attacks, with ongoing research into new treatments that could reduce reliance on liver transplants for chronic patients.
Hepatocellular carcinoma in acute hepatic porphyrias: A Damocles Sword.
Mol Genet Metab
November 2019
UMRs 1149, Centre de Recherche sur l'Inflammation, Institut National de la Santé et de la Recherche Médicale, F-75018 Paris, France; Assistance Publique-Hôpitaux de Paris, HUPNVS Centre Français des Porphyries, Hôpital Louis Mourier, 178 Rue des Renouillers, F-92701 Colombes, France; Laboratory of Excellence Gr-Ex, France; Université Paris Diderot, UFR de Médecine Xavier Bichat, F-75018 Paris, France.
Article Synopsis
- Porphyrias are genetic disorders that disrupt the heme biosynthesis pathway and include acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria, which are linked to an increased risk of liver cancers, particularly hepatocellular carcinoma (HCC).
- The incidence of HCC in patients with acute hepatic porphyrias ranges from 0.16% to 0.35%, with higher rates observed in older populations living in Sweden and Norway due to genetic factors.
- The study explores the potential causes of HCC in these patients, emphasizes the need for regular imaging screenings for those over 50, and discusses the utility of a new non-invasive marker, PIVKA-II, for monitoring liver
[Porphyrias-what is verified?].
Internist (Berl)
December 2018
MVZ Labor PD Dr. Volkmann und Kollegen GbR, 76133, Karlsruhe, Deutschland.
Article Synopsis
- Porphyrias are disorders caused by enzyme defects in heme biosynthesis, classified into acute and non-acute types based on their symptoms and affected pathways.
- Acute hepatic porphyrias lead to severe symptoms like abdominal pain and neurological issues, with key indicators being elevated levels of 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine.
- Non-acute porphyrias, such as porphyria cutanea tarda (PCT) and erythropoietic protoporphyria (EPP), mainly cause skin photosensitivity and may result in liver damage, with treatments including iron depletion, chloroquine, and new therapies in clinical trials.
Acute hepatic and erythropoietic porphyrias: from ALA synthases 1 and 2 to new molecular bases and treatments.
Curr Opin Hematol
May 2017
aINSERM U1149 CNRS ERL 8252, Centre de Recherche sur l'inflammation, Université Paris Diderot, site Bichat, Sorbonne Paris Cité bLaboratory of excellence, GR-Ex, Paris cAP-HP, Centre Français des Porphyries, Hôpital Louis Mourier, Colombes dAP-HP, Hôpital Beaujon, Service de Biochimie Clinique, Clichy, France.
Article Synopsis
- Recent studies have uncovered new genes and mechanisms related to inherited diseases affecting the heme biosynthetic pathway, including a newly characterized condition called X-linked protoporphyria, which is expected to see innovative treatments soon.
- The establishment of clinical and biological porphyria networks has enhanced patient follow-up, revealing new mutated genes and long-term complications, while a potential RNAi-based treatment targeting hepatic ALAS1 is currently being tested for acute hepatic porphyrias.
- Understanding genetic variations and regulatory processes surrounding heme biosynthesis has advanced significantly, creating new opportunities for managing erythropoietic and acute hepatic porphyrias.
Acute Porphyrias.
J Emerg Med
September 2015
Department of Medicine, University of Connecticut, Farmington, Connecticut; Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Article Synopsis
- Porphyrias are metabolic disorders affecting heme biosynthesis, categorized into acute (inducible) and chronic cutaneous porphyrias, with acute hepatic porphyrias including types like acute intermittent porphyria (AIP) and ALADP.
- AIP is the most common acute form, presenting with nonspecific symptoms primarily abdominal pain, along with hyponatremia and hypomagnesemia that can lead to seizures in about 20-30% of cases.
- Diagnosis is quick using random urinary porphobilinogen tests, and treatment involves stopping harmful medications and administering intravenous heme and glucose during emergency attacks, leading to a generally good prognosis with early recognition.