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The Netherlands Journal of Medicine Jul 2020Porphyrias are rare metabolic disorders. Lack of awareness and knowledge about the clinical features of porphyrias results in diagnostic and therapeutic delays for many... (Review)
Review
Porphyrias are rare metabolic disorders. Lack of awareness and knowledge about the clinical features of porphyrias results in diagnostic and therapeutic delays for many patients. Delays in diagnosing and treating porphyrias can result in severe, progressive morbidity (and mortality) and psychological distress for patients. This review discusses the pathophysiology, diagnosis, treatment, and follow-up of the most prevalent porphyrias: acute intermittent porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria.
Topics: Delayed Diagnosis; Humans; Porphyria Cutanea Tarda; Porphyria, Acute Intermittent; Porphyrias; Practice Guidelines as Topic; Time-to-Treatment
PubMed: 32641543
DOI: No ID Found -
Diagnostics (Basel, Switzerland) Jul 2021Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in... (Review)
Review
Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.
PubMed: 34441276
DOI: 10.3390/diagnostics11081343 -
Journal of Clinical and Experimental... 2022Skin manifestations of systemic disorders give a clue to the organ involved and help identify the possible disease-causing injury. Skin changes of liver cirrhosis are... (Review)
Review
Skin manifestations of systemic disorders give a clue to the organ involved and help identify the possible disease-causing injury. Skin changes of liver cirrhosis are not specific, as they may be seen in disorders not involving the liver. Thus, a constellation of skin changes along with systemic features may help us to identify the disease-causing liver cirrhosis. Pruritus is one of the most common and distressful symptoms of liver cirrhosis, severely affecting the quality of life, which further necessitates understanding cutaneous manifestations of cirrhosis. Other nonspecific cutaneous manifestations include spider telangiectasia, palmar erythema, paper money skin, xanthomas, pigmentation changes, nutritional deficiencies, hair changes, and nail changes. This review discusses the nonspecific skin manifestations associated with liver cirrhosis followed by specific cutaneous findings seen in common diseases causing liver cirrhosis, such as viral infections, biliary tract disorders, chronic alcoholism, and metabolic disorders. Early recognition of cutaneous features can help prevent or delay the development of complications and end-stage disease, decreasing morbidity and mortality.
PubMed: 35814509
DOI: 10.1016/j.jceh.2021.12.013 -
Photodiagnosis and Photodynamic Therapy Jun 2022Erythropoietic protoporphyria (EPP) is caused by deficiency of the enzyme converting protoporphyrin IX (PpIX) into heme resulting in accumulation of PpIX; leading to... (Review)
Review
BACKGROUND
Erythropoietic protoporphyria (EPP) is caused by deficiency of the enzyme converting protoporphyrin IX (PpIX) into heme resulting in accumulation of PpIX; leading to photosensitivity and liver toxicity. Cimetidine might inhibit δ-aminolevulinic acid synthase influencing the heme biosynthesis. We present cases with EPP treated with cimetidine at our department, and a literature review.
METHODS
Systematic searches were performed to identify literature describing EPP patients treated with cimetidine. On that ground we treated EPP patients with cimetidine through spring and summer in 2020 and 2021 at our department. Their erythrocyte PpIX level and standard blood and liver parameters were collected before and during 4 months of treatment. Using a questionnaire, patients were asked about change in photosensitivity, side effects, and whether they would like to resume treatment in the spring of 2022.
RESULTS
Literature searches identified 9 patients treated with cimetidine. Four were outpatients reporting decreased photosensitivity. At our department 18 outpatients started treatment. Fifteen used oral cimetidine daily for 4 months or more providing a significant decrease in erythrocyte PpIX with a median of 20% (range: -18% to 53%) after 4 months. Eleven of the 15 patients reported a decrease in photosensitivity during treatment, 3 patients were unsure, and 1 patient experienced unchanged photosensitivity. Only mild side effects were reported. Fourteen patients requested to resume treatment in the spring of 2022.
CONCLUSIONS
These cases suggest that cimetidine can lower erythrocyte PpIX in patients with EPP.
Topics: Cimetidine; Ferrochelatase; Heme; Humans; Photochemotherapy; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins
PubMed: 35245673
DOI: 10.1016/j.pdpdt.2022.102793 -
Translational Gastroenterology and... 2021The acute hepatic porphyrias (AHP) are a group of four inherited diseases of heme biosynthesis. They present with similar severe, episodic, acute neurovisceral symptoms... (Review)
Review
The acute hepatic porphyrias (AHP) are a group of four inherited diseases of heme biosynthesis. They present with similar severe, episodic, acute neurovisceral symptoms due to abnormally elevated levels of porphyrin precursors delta-aminolevulinic acid (ALA). Recently genetic screening indicates that the prevalence of mutation carrier state is more common than previously thought, occurring in 1 in 1,500, though the clinical penetrance of symptomatic AHP is low at ~1%. Symptomatic attacks occur primarily in females during their reproductive years. In an acute porphyria attack, the primary symptom is abdominal pain, due to intestinal dysmotility from autonomic nerve injury. Other manifestations include seizures, weakness and mood changes, point to injury involving peripheral and central nervous system. Due to the non-specific nature of the symptoms and signs in AHP, the diagnosis is often delayed by many years. The diagnosis of AHP depends on biochemical evidence of elevated ALA and PBG levels in urine during symptomatic attacks. Genetic testing is used for confirmation of the gene involved and the exact mutation. Treatment involves administration of heme, which downregulates production of ALA. Long-term management centers on educating genetic carriers on avoiding triggers that increase the risk of acute attacks and screening family members.
PubMed: 33824928
DOI: 10.21037/tgh-2020-01 -
Diagnostics (Basel, Switzerland) Jan 2022Iron is a trace element that is important for many vital processes, including oxygen transport, oxidative metabolism, cellular proliferation, and catalytic reactions.... (Review)
Review
Iron is a trace element that is important for many vital processes, including oxygen transport, oxidative metabolism, cellular proliferation, and catalytic reactions. Iron supports these functions mainly as part of the heme molecule. Heme synthesis is an eight-step process which, when defective at the level of one of the eight enzymes involved, can cause the development of a group of diseases, either inherited or acquired, called porphyrias. Despite the strict link between iron and heme, the role of iron in the different types of porphyrias, particularly as a risk factor for disease development/progression or as a potential therapeutic target or molecule, is still being debated, since contrasting results have emerged from clinical observations, in vitro studies and animal models. In this review we aim to deepen such aspects by drawing attention to the current evidence on the role of iron in porphyrias and its potential implication. Testing for iron status and its metabolic pathways through blood tests, imaging techniques or genetic studies on patients affected by porphyrias can provide additional diagnostic and prognostic value to the clinical care, leading to a more tailored and effective management.
PubMed: 35204362
DOI: 10.3390/diagnostics12020272 -
Life (Basel, Switzerland) Apr 2024Porphyria denotes a heterogeneous group of metabolic disorders caused by anomalies in the biosynthesis of heme, a crucial component of hemoglobin and other vital...
Porphyria denotes a heterogeneous group of metabolic disorders caused by anomalies in the biosynthesis of heme, a crucial component of hemoglobin and other vital hemoproteins [...].
PubMed: 38792603
DOI: 10.3390/life14050581