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All Diseases > Porphyrias
Disease Category: Porphyrias
The porphyrias are a group of rare, inherited disorders caused by problems with one of eight enzymes necessary for the production of heme, an important component of hemoglobin and other proteins. The porphyrias are classified as either acute hepatic or cutaneous; the former are characterized by acute attacks of severe abdominal pain accompanied by nausea, vomiting and other symptoms, whereas the latter have various symptoms, including blistering or burning in response to sun exposure.
Research groups studying this disease
Porphyrias Consortium (PC)View Disease Definition
The porphyrias are a group of rare metabolic diseases that may present in childhood or adult life and are due to deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias have various symptoms depending on the type, but these can range from neurological symptoms to sun sensitivity. See the descriptions of each type to get more information. The natural history of these disorders is not well described and it is not known why some patients are more severe than others. Therefore, the purpose of this long-term follow-up study is to collect a large group of patients with the different types of porphyria and to provide a better understanding of the natural history of these disorders. The hope is that this information will help in developing new forms of treatment. The research aims are: 1. To study the prevalence of specific indicators of disease severity. To study the effects on quality of life and health of various porphyrias. 2. To determine the relationships between disease severity and various biological characteristics, genetic information, and environmental factors.
The purpose of this study is to collect information on acute porphyria attacks that may have been caused by a medication. Individuals who have tested positive for an acute porphyria, or have been told by a doctor that they may have the disease may join this study. We are particularly interested in the following: (1) Attacks that appeared to be due to a specific medication; (2) Use of a medication that is considered risky in porphyria but caused no problems; and (3) Use of medications for which the safety profile in porphyria is unknown.
7211: Effect of Oral Cimetidine in the Protoporphyrias
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are genetic defects of heme biosynthesis that cause life-long, painful cutaneous sensitivity to light. EPP and XLP, collectively called the protoporphyrias, result in the accumulation of the light-sensitive molecule protoporphyrin IX initially in the bone marrow during hemoglobin synthesis and secondarily in erythrocytes, plasma, and the liver. In addition to photosensitivity, protoporphyria can also result in anemia, gallstones, and liver failure. No therapy has been demonstrated to reduce protoporphyrin levels or prevent the potentially life-threatening complications of EPP. Cimetidine has gained attention as a possible treatment for human porphyrias because of a potential off-target effect of inhibition of delta-aminolevulinate synthase (ALAS), the first enzyme of heme biosynthesis. The objective of this study is to determine the efficacy and safety of oral cimetidine administration in the protoporphyrias. Efficacy will be based on protoporphyrin levels, photosensitivity, and quality of life questionnaires. If the results are positive, this would be the first study providing quality evidence for an agent acting as a disease-modifying therapy for EPP. The study is also attractive because it repurposes an already approved drug with few side effects to treat a rare human disease.
AIP is rare a genetic disorder caused by mutations in the hydroxymethylbilane synthase gene (HMBS) that reduce the function of an enzyme (a type of protein) in the body that is necessary for the production of heme. Heme is important for your body to use oxygen and for your liver to work properly. When a person does not produce enough of this enzyme, substances called ALA and PBG can accumulate, and this can cause symptoms of AIP. These symptoms may include abdominal pain; pain in the arms, legs and back; muscle weakness; nausea and vomiting; and confusion, hallucinations, and seizures. A small portion of AIP patients have recurrent attacks, while many others who have a mutation in the HMBS gene never develop symptoms. The purpose of this research study is to learn more about genetic factors (specific patterns in a gene) that predispose or protect an individual with a change (or mutation) in the gene that causes Acute Intermittent Porphyria (AIP) to develop symptoms.
Not Yet Recruiting
The purpose of this study is to establish an independent, public, online database, called the International Porphyria Molecular Diagnostic Database. This Database will have all published, newly identified, and biochemically/clinically verified pathogenic mutations for the eight major porphyrias, as well as a list of genomic variants for each gene from the latest genomic/exonic databases (e.g., GnomAD) that are benign, likely-benign, or unknown. The eight major porphyrias include: Acute Intermittent Porphyria (AIP), due to pathogenic mutations in the Hydroxymethylbilane Synthase (HMBS) gene, Hereditary Coproporphyria (HCP), due to pathogenic mutations in the Coproporphyrinogen Oxidase (CPOX) gene, Variegate Porphyria (VP), due to pathogenic mutations in the Protoporphyrinogen Oxidase (PPOX) gene, Porphyria Cutanea Tarda (PCT) due to pathogenic mutations in the Uroporphyrinogen Decarboxylase (UROD) gene, Erythropoietic Protoporphyria (EPP) due to pathogenic mutations in the Ferrochelatase (FECH) gene, Congenital Erythropoietic Porphyria (CEP) due to pathogenic mutations in the Uroporphyrinogen III Synthase (UROS) gene, X-Linked Protoporphyria (XLP) due to pathogenic mutations in the Aminolevulinic Acid Synthase 2 (ALAS2) gene, and ALA-Dehydrogenase Deficient Porphyria (ADP), due to pathogenic mutations in the ALADehydrogenase (ALAD) gene. Efforts will be directed to verify each published or new mutation in conjunction with the European Porphyria Network (EPNET) by elevated urinary, stool, erythrocyte, or plasma porphyrin precursor levels as well as by specific enzymatic activity, when available, from de-identified patients with the respective clinical manifestations for each porphyria.
Committed to improving the quality of life of the porphyria patient community, relentlessly focused on advancing disease awareness, research, and therapies in all the porphyrias.