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Patients with porphyria cutanea tarda (PCT) reveal a susceptibility to reversible inactivation of hepatic uroporphyrinogen decarboxylase, which might be triggered by alcohol, hepatitis C virus infection, and iron overload. Inherited factors that may predispose to clinically overt PCT also include sequence deviations in the HFE gene that is mutated...
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Context 1
... the 51 PCT patients studied, 8 (15.7 %) were heterozygous for mutation C282Y in the HFE gene and 4 (7.8 %) were homozygous for this mutation (Table 1). Eighteen patients (35.3 %) were heterozygous for the H63D mutation and 2 (3.9 %) were homozygous carriers of this mutation. ...
Similar publications
Porphyria cutanea tarda (PCT) occurs in sporadic (sPCT) and familial (fPCT) forms, which are generally clinically indistinguishable and have traditionally been differentiated by erythrocyte uroporphyrinogen decarboxylase (UROD, EC 4.1.1.37) activity. We used UROD gene sequencing as the reference standard in assessing the diagnostic accuracy of UROD...
Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil.
Investigation of porp...
Citations
... 3 PCT could be triggered by alcohol, excessive vitamin C intake, oral contraceptives, hepatitis C infection and iron overload coupled with underlying genetic susceptibility. 4 During the COVID-19 pandemic, COVID-19 has been identified as a 6 However, there is currently insufficient evidence to link COVID-19 infection with PCT. Our patient was tested negative for COVID-19 and her PCT is most likely caused by iron overload from undiagnosed haemochromatosis. ...
... Despite a proven relationship between PCT and haemochromatosis in the medical literature, diagnosing PCT can be difficult due to its diverse aetiologies and may result in a missed diagnosis. 4 The pathogenesis relating the two conditions necessitates the understanding of haem synthesis in addition to the effects of iron metabolism on the pathway. ...
We present a case of a woman who presented with a photosensitive skin rash and blisters on her extremities which did not improve with steroids. These were associated with polyarthralgia and a deranged liver function test on her admission. Further workup revealed that the patient has an undiagnosed porphyria cutanea tarda (PCT) and hereditary haemochromatosis. The patient later underwent regular venesections which improved her condition. This case report not only illustrates the challenge in diagnosing PCT but also aims to highlight the association between PCT and hereditary haemochromatosis.
... Hemochromatosis is one of the most frequent autosomal recessive hereditary diseases in European Caucasians with a prevalence of 1:200 to 1:500. 1 Porphyrias are clinically and genetically heterogeneous metabolic diseases arising from predominantly inherited catalytic deficiencies of specific enzymes involved in heme biosynthesis. ...
... l consumption and HCV infection appears to enhance formation of the URO-D inhibitor by mediating oxidative liver injury. The correlative relationship between HFE C282Y genotype and PCT in the current study supports our previous observations[7] and those of others[20] however, conflicting data surround the relationship between HFE H63D and PCT risk.[21] In a study involving fewer patients, we observed a non-significant trend toward enrichment of HFE H63D among patients with fPCT.[7] In that study, the frequency of HFE H63D was set at 15.9% (vs. 13.7% in the current study, Table 1). Some investigators have observed a higher frequency of HFE H63D among patients with PCT while others have ...
Both familial and sporadic porphyria cutanea tarda (PCT) are iron dependent diseases. Symptoms of PCT resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y, c.843G>A, rs1800562) that enhances iron aborption by reducing hepcidin expression is a risk factor for PCT. Recently, a polymorphic variant (D519G, c.1556A>G, rs11558492) of glyceronephosphate O-acyltransferase (GNPAT) was shown to be enriched in male patients with type I hereditary hemochromatosis (HFE C282Y homozygotes) who presented with a high iron phenotype, suggesting that GNPAT D519G, like HFE C282Y, is a modifier of iron homeostasis that favors iron absorption. To challenge this hypothesis, we investigated the frequency of GNPAT D519G in patients with both familial and sporadic PCT. Patients were screened for GNPAT D519G and allelic variants of HFE (both C282Y and H63D). Nucleotide sequencing of uroporphyrinogen decarboxylase (URO-D) identified mutant alleles. Patients with low erythrocyte URO-D activity or a damaging URO-D variant were classified as familial PCT (fPCT) and those with wild-type URO-D were classified as sporadic PCT (sPCT). GNPAT D519G was significantly enriched in the fPCT patient population (p = 0.0014) but not in the sPCT population (p = 0.4477). Both HFE C282Y and H63D (c.187C>G, rs1799945) were enriched in both PCT patient populations (p<0.0001) but showed no greater association with fPCT than with sPCT.
Conclusion:
GNPAT D519G is a risk factor for fPCT, but not for sPCT.
... Southern Brazil was colonized mostly by German and Italian people. The German prevalence of this mutation is 19% in the control group (33) , however, Portugal and Spain also present frequencies around 20% in the general population (16,(34)(35)(36)(37) . Italy showed a prevalence ranging from 12.6% to 14.7% (25)(26)(27)(28)38) , which, contrary to expectations, is slightly lower than the one in this study. ...
Hereditary hemochromatosis (HH) is an autosomal recessive disorder caused by mutations in the HFE gene; it is characterized by the risk of iron overload. C282Y and H63D are the most associated mutations in HH. This study aimed to determine the frequency of mutations in the south of Brazil and São Paulo. It used the real-time polymerase chain reaction (PCR) technique and the results collected from Genolab data. In 90 individuals, 46.67% had at least one of the mutations for HH. There is a high prevalence of these mutations in both populations, therefore searching for patients under clinical suspicion is recommended.
... 16 In Germany and USA the frequency of C282Y and H63D mutations is higher in patients suffering from PCT, compared to control population. 11,17,18 However, in one of the studies conducted in Germany no difference was observed in the frequency of H63D mutation. 18 France and Portugal presented a greater frequency of C282Y mutation in the normal population in the North rather than in the South, probably due to the increased influence of Celtic origin in the North. ...
... 11,17,18 However, in one of the studies conducted in Germany no difference was observed in the frequency of H63D mutation. 18 France and Portugal presented a greater frequency of C282Y mutation in the normal population in the North rather than in the South, probably due to the increased influence of Celtic origin in the North. 19,20 The role of S65C mutation does not appear to be decisive in PCT, as studies demonstrate that prevalence was no different between patients suffering from PCT and the control group. ...
Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil.
Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations.
An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR.
Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors.
Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients.
... The relevance of this error is not only of issue when predicting the incidence of recessive disorders in any given population, but also for studies that rely on correctly identifying the expected frequency of homozygosity, such as homozygosity mapping. Many studies make use of the Hardy–Weinberg expectation to estimate the prevalence of compound heterozygotes within a study population (Ferreira et al. 2008; Beutler et al. 2002, Frank et al. 2006), but few factor in the effects of inbreeding despite the knowledge that the populations are indeed consanguineous (Carrasquillo et al. 1997; Caron et al. 2003). Indeed, approaches that take explicit account of the influence of inbreeding on the expected frequency of compound heterozygotes are few and recent (ten Kate et al. 2010). ...
... Hemo- chromatosis is the most common inherited liver disease and the most common autosomal recessive genetic disorder [4]. From epidemiological point of view there is a clearcut association between PCT and hemochromatosis [5]. The question rises how porphyria, hemochromatosis and/or the hemolytic streptococcal infection can be linked together. ...
We present a 27-year-old female Caucasian patient, who initially presented with extensive fragility and blistering of mainly the dorsal side of both hands. Histology and urine porphyrin analysis confirmed the diagnosis of porphyria cutanea tarda. Internal screening for underlying disease revealed C282Y mutation-associated primary hemochromatosis, a hereditary iron-overload syndrome that may cause toxicity of a variety of organs. Hemochromatosis and porphyria cutanea tarda are pathogenetically linked as iron interferes with heme synthesis pathway. Patient was successfully treated with phlebotomy and low-dose hydroxychloroquine.
Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non‐English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence‐based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun‐exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.
Purpose. To study the frequency of genotypes and alleles of C282Y and H63D mutations in the HFE gene in patients with porphyria cutanea tarde of the West Siberian region and their influence on the clinical and biochemical characteristics of the disease. Materials and methods. We observed 14 patients with porphyria cutanea tarde (PCT), who underwent a comprehensive general clinical and instrumental examination. The indicators of the excretory profile of porphyrin metabolism indicators were purposefully determined, a molecular genetic examination was carried out to determine the genotypes and alleles of the C282Y and H63D mutations of the hemochromatosis gene HFE. Results and discussion. Molecular genetic research found that the HFE gene mutation was found in 7 patients (50.0%). Polymorphism for the C282Y allele was found in 2 (14.3%) patients, and for the H63D allele - in 5 patients (35.7%). Risk factors for the manifestation of PCT included frequent alcohol consumption and chronic HCV infection. Genotype 1b was recorded more often (9 people), less often - genotype 3a (4 people). The excretory profile of porphyrin metabolism indices in patients of both groups exceeded the control values. Porphyrin metabolism parameters in patients without HFE gene mutations were significantly higher than those in patients without HFE gene mutations. Conclusions. Polymorphism of the hemochromatosis gene HFE in PCT was detected in 50% of patients. The most common mutation was the H63D allele. The level of porphyrin metabolism disorders in patients with HFE hemochromatosis gene mutations is significantly lower. The clinical picture of PCT in all observed patients did not differ. Chronic viral hepatitis C is assessed as a risk factor for the manifestation of PCT.
