HFE Gene Mutations Research Articles

HYPERFERRITINEMIA ASSOCIATED WITH HFE GENE MUTATIONS (H63D, C282Y, AND S65C) IN BRAZIL

HYPERFERRITINEMIA ASSOCIATED WITH HFE GENE MUTATIONS (H63D, C282Y, AND S65C) IN BRAZIL

Hemochromatosis-How Not to Overlook and Properly Manage "Iron People"-A Review.

Hemochromatosis (HC) is the main genetic disorder of iron overload and is regarded as metal-related human toxicosis. HC may result from HFE and rare non-HFE gene mutations, causing hepcidin deficiency or, sporadically, hepcidin resistance. This review focuses on HFE-related HC. The illness presents a strong biochemical penetrance, but its prevalence is low. Unfortunately, the majority of patients with HC remain undiagnosed at their disease-curable stage. The main aim of HC management is to prevent iron overload in its early phase and remove excess iron from the body by phlebotomy in its late stage. Raising global awareness of HC among health staff, teaching them how not to overlook early HC manifestations, and paying attention to careful patient monitoring remain critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

HFE Gene Mutations as Predisposing Factors for Childhood Acute Lymphoblastic Leukaemia in Iraqi Patients

Hemochromatosis is a prevalent hereditary disorder that causes excess iron to build up in the body to dangerous levels. Hereditary hemochromatosis, also known as HFE-related hemochromatosis is carried on by changes in the HFE gene. Investigating the gene mutations of the HFE gene is a way to explore the prevalence of this disease. This study aims to determine the association between hemochromatosis HFE gene mutations (C282Y and H63D) and childhood acute lymphoblastic leukaemia in patients at Basra Specialized Hospital for Children and AL-sadder Teaching Hospital in the Basra governance. QIAamp DNA and Blood Mini Kit were used to isolate and identify Human genomic DNA and detect mutations in the HFE gene using the DNA hybridization method. In this study, the absence of the C282Y mutations in both patients and the control group was identified. However, testing DNA-based hybridization experiments revealed low detection levels of the H63D (homozygous, heterozygous) mutations; in only 12.5% of patients. The H63D (only homozygous) mutations were present in 10% of the control group. The association between patients and the control group is considered statistically significant. The HFE gene mutations (C282Y and H63D), originate in acute lymphoblastic leukaemia in childhood, thus, this study recommends complementary investigations to illustrate this case in more detail with more cases of patients and discover the hidden agents underlying these mutations.

Investigation of BMP6 mutations in Brazilian patients with iron overload

BackgroundIron overload (IO) is a complex condition in which clinical, behavioral and genetic factors contribute to the phenotype. In multiethnic and non-Caucasian populations, mutations in HFE gene alone cannot explain IO in most of the cases, and additional genetic and environmental factors must be investigated. Bone Morphogenetic Proteins (BMPs) play a central role in iron homeostasis by modulating HAMP transcription through the signaling pathway that includes SMAD and HJV. In this study, we aimed to explore the clinical relevance of BMP6 mutations in a cohort of Brazilian patients with IO. Methods41 patients with IO were evaluated. Blood samples were collected to analyze BMP6 mutations through New Sequence Generations (NGS). Frequency of variants and mutations were analyzed and correlated with clinical and environmental characteristics. ResultsWe identified BMP6 mutations in three patients with IO. The p.Arg257His mutation was identified in two patients and the p.Leu71Val mutation was identified in one patient. Two of these patients had additional risk factors for IO (HFE mutations and diabetes mellitus). ConclusionBMP6 mutations, when combined to other genetic and clinical risk factors, may contribute to IO. Functional studies and THE evaluation of large cohorts are necessary to fully address BMP6 role in IO.

Self-Sustainability with Therapeutic Phlebotomy, a Solution to the National Blood Crisis?

CONCLUSION Hereditary hemochromatosis (HH) is a genetic condition associated with iron overload in the human body. The mainstay of treatment remains therapeutic phlebotomy. On August 1st, 2022, the American Red Cross approved using blood obtained from therapeutic phlebotomy for transfusion. While normal individuals can donate blood only as often as once in 56 days, individuals with HH can have phlebotomy as often as once weekly. Utilizing the blood collected from these patients could be a significant resource to mitigate the shortage of blood needed for transfusion. We aimed to quantify the number of units of blood removed by therapeutic phlebotomy from individuals with HH and assess its potential contribution to total units of blood required in a community hospital for two years (2021 and 2022). We retrospectively reviewed electronic medical records of adult individuals who underwent therapeutic phlebotomy at Saint Vincent Hospital between January 1, 2021, and December 31, 2022. Patients with hereditary hemochromatosis were identified based on a positive genetic test for HFE gene mutations. We collected data including gender, race, age at diagnosis, and the number of units of blood removed from patients during the study period. The total number of units transfused in the in-patient care services and operating room was obtained. A descriptive statistic was performed using R version 4.2.2 statistics software. A total of 112 patients received therapeutic phlebotomy over two years (2021 and 2022) of whom 65% (N=73) had a diagnosis of HH. A majority of the patients were males (60%, 44/73) and were non-Hispanic/Latino (85%, 62/73). The mean age at diagnosis of HH was 62 [standard deviation (SD): 17] years. The median number of units of blood removed by phlebotomy per patient with HH was 3 (2-5), the annual distribution is as displayed in Table 1. A total of 504 units of whole blood was removed through therapeutic phlebotomy from 73 patients during the study period. The total requirement for blood transfusion across all the departments in the hospital was 6065 units (2,733 units in 2021 and 3,332 units in 2022). The total number of units removed through therapeutic phlebotomy in HH patients represented 8.31% (504/6065 Units) and 82.49% (504/611 Units) of total units of blood requirement for the entire hospital and operating room respectively (Table 2). The units of blood removed through therapeutic phlebotomy of patients with HH, could potentially help sustain 8.31% of total blood requirement of the hospital. Primarily, over 82% of the demand from the operating room could be fulfilled if the entirety of the blood from therapeutic phlebotomy were to be transfused. Overcoming technical challenges in utilizing the blood from therapeutic phlebotomy for transfusion in routine clinical practice could help mitigate the national blood crisis and aid in self-sustainability of blood products at a community level. Our study highlights the need for broader efforts to create awareness and incentivizing re-utilization of blood obtained from therapeutic phlebotomy.

HFE hemochromatosis gene polymorphism and porphyria cutanea tarda

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.

Screening for Hereditary Hemochromatosis in Newly Referred Diabetes Mellitus

AimsHereditary hemochromatosis (HH) is the most common inherited disease in European populations. It is particularly common in people of Irish heritage, approximately 2% of whom will be at risk of iron overload as a result of human homoeostatic iron regulator protein (HFE) gene mutations. We aimed to evaluate the utility of screening for HH in newly referred patients with DM of Irish heritage in a prospective study. MethodsOf 575 patients newly referred between March 2018 and March 2021, 556 attended for blood testing, to include fasting transferrin saturations, prior to their first clinic visit. Patients with elevated transferrin saturations were further screened for hereditary hemochromatosis (HH) with HFE gene analysis. ResultsTransferrin saturations were elevated in 13 of 556 patients (2.3%), 3 of whom had a preexisting diagnosis of HH. Of the remaining 10 patients, 7 had HFE gene mutations suggestive of HH (2 C282Y homozygous, 3 C282Y/H63D compound heterozygous, and 2 H63D homozygous), 1 was a HH carrier (C282Y heterozygous), and 2 had normal genetics. ConclusionsThe prevalence of HH of 1.8% in this screened DM population is lower than the reported incidence of HH in the Irish population, suggesting a limited utility of routine screening for HH in newly referred patients with DM.

Hereditary hemochromatosis: An update vision of the laboratory diagnosis

Haemochromatosis (HC) is an inherited disorder of iron metabolism. The 85–90% of Hereditary hemochromatosis cases are caused by mutations in HFE gene (HC type 1). The remaining 10–15% of HC cases are caused by mutations in other non-HFE genes (HJV, HAMP, TRF2, SLC40A1, BMP6). The study of patients for the diagnosis of HC has an important laboratory approached: analysis of biochemical parameters and genetic studies. To confirm a case, it is necessary to carry out a genetic study of the C282Y and H63D mutations. The presence of C282Y mutation in homozygosis is compatible with the diagnosis of HC type 1. Due to the incomplete penetrance of this mutation and the variable phenotypic expression, the severe forms of the disease are relatively rare. The study of variants in non-HFE genes allows more detailed study of both non-classic HC cases and those with more severe clinical expression. The genotype characterization of a patient not always justified the phenotype expression of the symptoms in this disease. All laboratory clinicians must consider recommendation provide by the experts in the Materia.

5613463 PREVALENCE OF HEMOCHROMATOSIS HFE GENE POLYMORPHISM AMONG EGYPTIAN βTHALASSEMIA PATIENTS AND ITS RELATION TO DEVELOPMENT OF DIABETES MELLITUS

Background: β-thalassemia constitutes a major health problem in Mediterranean countries. Impaired glucose tolerance and diabetes mellitus are observed complications in patients with thalassemia. However, the mechanisms leading to diabetes are still poorly understood.H63D gene polymorphism, is the second variant of hemochromatosis (HFE) gene, that causes hemochromatosis. Aims: We aimed to assess the frequency of diabetes mellitus in β -thalassemia patients and the frequency of H63D gene polymorphism as well as its relation to development prediabetes and diabetes mellitus in β -thalassemia patients. Methods: Case control study was conducted on 50 patients with β-thalassemia and 50 healthy control with matched age and sex. The age ranged from 6-18y. Study subjects were investigated with oral glucose tolerance test, fasting C-Peptide, fasting insulin, anti -gad and screened for frequency of H63D mutation of HFE gene using restriction fragment length polymorphism. Results: 32% of patients had normal glycemic state, 52% had impaired glucose tolerance and 16% were diabetic P<0.001. H63D mutation was more frequent in thalassemia patient. GG genotype was significantly higher in β- thalassemia patients versus healthy controls (68%vs24%) P<0.001. GG genotype was prevalent in 77%and 75% of prediabetes and diabetic thalassemia patients respectively, versus 50% in patients with normal glycemic state P<0.001. Conclusions: GG genotype of H63D mutation of hemochromatosis HFE gene was frequent in our β- thalassemia patients which may be considered as a genetic risk factor for development of impaired glucose tolerance and diabetes in patients with. β-thalassemia. Keywords: thalassemia; diabetes; HFE gene mutation

Effect of HFE Gene Mutations on Iron Metabolism of Beta-Thalassemia Carriers

The human hemochromatosis protein HFE is encoded by the HFE gene and participates in iron regulation. The aim of this study was to detect the most frequent HFE gene mutations in a control population and in β-thalassemia trait (BTT) carriers, and to study their relationship with iron metabolism. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA2 quantification, iron (Fe), total Fe binding capacity and ferritin were assayed. HFE gene mutations were analyzed by real-time PCR. A total of 119 individuals (69 normal and 50 BTT) were examined. In the control group, 9% (6/69) presented a codon 282 heterozygous mutation (C282Y), and 19% a codon 63 mutation (H63D) (13/69, 11 heterozygotes and 2 homozygotes). In the BTT group, 3 carriers (6%) were heterozygous for C282Y, 14 (28%) for H63D, 1 (2%) for a codon 65 mutation and 1 (2%) was H63D and C282Y double heterozygous. Control group Fe metabolism did not show significant differences (p &gt; 0.05) according to whether or not they carried an HFE gene mutation; while the BTT group with and without HFE mutation showed higher Fe and ferritin than the control group (p &lt; 0.05). However, no increases in iron parameters were detected in BTT carriers that simultaneously exhibited an H63D mutation compared to BTT subjects without a mutation. Therefore, the iron metabolism alterations observed in BTT carriers could not be attributed to the presence of HFE gene mutations. It is likely that BTT individuals have other genetic modifiers that affect their iron balance.

S3017 HIV-Associated Iron Overload: A Rare Cause of Elevated Transaminases in Patients With HIV

Introduction: Hereditary hemochromatosis can lead to elevated transaminases due to iron deposition in liver. In this case, we discuss a patient with advanced HIV, who in the absence of HFE gene mutation or history of blood transfusions, had drastically elevated ferritin levels and evidence of hemosiderosis in the liver. Case Description/Methods: A 44-year-old man with a medical history notable for HIV (diagnosed 15 years ago, not on antiretroviral therapy, CD4 count 0, viral load 799000) presented with a transient ischemic attack which resolved after tPA. He was incidentally found to have elevated transaminases and admitted for workup. Patient denied alcohol use for the past 4 years. Physical exam was unremarkable with BMI 17. Labs were notable for ALT 150 u/L, AST 320 u/L, ALP 431 u/L, GGT 1056 u/L, and total serum bilirubin 0.4 mg/dL. His liver enzymes were within normal limits until 3 months prior to presentation, when he was incidentally found to have ALT 165 u/L, AST 100 u/L, ALP 156 u/L, and total serum bilirubin 0.3 mg/dL. Of note, at that time, the patient had received a course of amoxicillin-clavulanate for pneumonia. Hepatitis panel was negative for active infection. DILI was suspected due to history of receiving amoxicillin-clavulonate; however, his liver enzymes were still uptrending 3 months after receiving the medication which is uncommon with DILI. AIDS cholangiopathy, a chronic development of biliary strictures caused by infection, was also suspected. MRCP showed no abnormality of biliary system but revealed iron deposition in the liver and spleen consistent with hemosiderosis. Iron studies were then performed showing ferritin 8260 ug/L, serum iron 157 ug/dL, TIBC 272 ug/dL, transferrin saturation 58%. HFE allele genetic testing was negative for mutation, and thus hereditary hemochromatosis was ruled out. Patient was sent home with outpatient hepatology follow-up. Discussion: HIV commonly targets cells that modulate iron metabolism such as macrophages, and consequently excessive iron accumulates in various organs including liver causing tissue damage, and thus the use of iron chelators has been proposed [1][2]. Our case illustrates the necessity of suspecting HIV-related iron overload in patients with HIV with elevated transaminases of unclear etiology as well as reiterates the potential implications of iron chelation therapy in such cases.

PB2251: TWO POLYCYTHEMIA VERA PATIENTS WITH A DIAGNOSIS OF CONCOMITANT HEREDITARY HEMOCHROMATOSIS

Background: Hereditary Hemochromatosis (HH) is an inherited iron metabolism disorder characterized by excessive iron accumulation in the liver, heart, pancreas and other endocrine organs. Although it is often associated with mutations in the HFE gene, it can also be caused by mutations associated with HJV, TFR-2 and ferroportin. JAK2 V617F (+) Polycythemia Vera (PV) is the most common cause of acquired primary erythrocytosis and has been reported very rarely in patients with HH. Aims: We presented two polycythemia vera patients with a diagnosis of concomitant hereditary hemochromatosis. Methods: Presence of HFE gene mutation and jak-2 V617F mutation was determined by PCR test Results: Case 1: N.G, a 67-year-old male patient with a history of hypertension, insulin-dependent diabetes mellitus and cerebrovascular accident was diagnosed with PV in another center in 2007. The patient was JAK2 V617F (+) and the tests performed in our laboratory after phlebotomies were EPO: 7.8 mIU/ml, ferritin: 34 ng/dl, transferrin saturation: 49%. Bone marrow aspiration biopsy revealed hypercellularity with erythroid and megakaryocytic hyperplasia. Although Hb/Hct levels were within the targeted range with hydroxyurea 500 mg 2x1 treatment, he was followed up with frequent phlebotomies due to persistent pruritus. After phlebotomy, there was a significant improvement in his pruritus. He was using clopidogrel as antiaggregant treatment. During follow-up, there was deterioration in blood glucose regulation and an increase in insulin requirement. In June 2018, he developed widespread hyperpigmentation on his skin. Due to unregulated diabetes, hyperpigmentation, and high ferritin levels despite frequent phlebotomy, he was examined for HH. He was found to be heterozygous positive for the HFE gene H63D mutation. The patient is still being followed up with HU 2X1 and phlebotomy without any problem. Case 2: E.H, a 57-year-old male patient with a history of hypertension and type 2 diabetes mellitus was diagnosed with PV in 2015. He was JAK2 V617F(+) and at diagnosis EPO:3.7 mIU/ml, ferritin:1403 ng/ml, transferrin saturation:63%. Bone marrow aspiration biopsy revealed hypercellularity and erythroid hyperplasia. Since he was a low-risk patient under the age of 60 and had no history of thrombosis, he was followed up with ASA 100 mg/day and intermittent phlebotomies. Similar to the first case, persistent pruritus was present despite the normal Hb/Hct level. Since hyperferritinemia was not expected in polycythemia vera and the patient was diabetic, he was examined for HH. In the HFE gene analysis, the H63D mutation was found to be heterozygous. Due to the frequent need for phlebotomy, the patient is considered to start treatment with hydroxyurea, and the follow-up still continues. Summary/Conclusion: The association of HH and PV has been rarely reported in the literature, and its clinical significance is not clearly known. In the presence of unexplained high ferritin levels in PV, even if the clinical findings are unclear, screening for HH may be recommended as an appropriate approach. The role of HFE genotypes in the development of myeloproliferative diseases is unknown. Clinical data accumulation is needed to elucidate iron metabolism and prognostic features in PV patients with HFE mutations. Keywords: polycythemia vera, hereditary hemochromatosis, JAK2 V617F, HFE mutation

Multiple organ lesion in hemochromatosis

AbstractPrimary hemochromatosis refers to a congenital autosomal recessive disease associated with a mutation of the homeostatic iron regulator (HFE gene), whose pathogenetic mechanism is increased iron absorption in the intestines, which leads to excessive accumulation of iron in organs and tissues, mainly in the liver, pancreas, heart, pituitary gland, testicles. The consequence of the disease is the development of fibrosis and insufficiency of these organs. Genotyping of HFE gene mutations is the main method of hemochromatosis verification. The presence of the C282Y/C282Y genotype in combination with iron overload manifestations is a diagnostic criterion of the disease. The basic treatment of patients with hemochromatosis is phlebotomy, which can be combined with the prescription of iron chelators, symptomatic therapy.A clinical case of primary hemochromatosis in a 48-year-old man is of interest due to long-term persistence of certain symptomatic manifestations of hemochromatosis and verification of the disease only after decompensation of a cardiovascular pathology and magnetic resonance imaging (MRI) of the thoracic cavity. After obtaining the final diagnosis and treatment, the patient showed positive dynamics of clinical symptoms, laboratory and instrumental data.

Iron accumulation is associated with periodontal destruction in a mouse model of HFE‐related haemochromatosis

To investigate the effect of Hfe gene mutation on the distribution of iron and periodontal bone loss in periodontal tissues. It remains unclear how tissue iron loading affects the periodontium architectures in a genetic animal model of hereditary haemochromatosis (HH). Male C57BL/6 Hfe -/- (8weeks old) and wild-type (WT) mice were utilized to examine the iron distribution in periodontal tissues, as well as periodontal tissues changes using micro-computed tomography and histomorphometric analysis. Furthermore, tissue inflammatory mediators, bone markers and periodontal pathogens were carried out in PFA-fixed paraffin-embedded tissues using ELISA, RT-qPCR and genomic DNA qPCR, respectively. Excessive iron deposition was found in the periodontal ligament, gingiva and alveolar bone in Hfe -/- mice relative to their WT counterparts. This, in turn, was associated with significant periodontal bone loss, increased cemento-enamel junction-alveolar bone crest distance and decreased expression of molecules involved in bone development and turnover. Furthermore, the pro-inflammatory cytokine - interleukin 6 and periodontal bacteria - Campylobacter rectus were significantly increased in Hfe -/- mice compared with WT controls. Our results suggest that the iron loading in a mouse model of HH decreases alveolar bone formation and leads to alterations in the inflammatory state in the periodontium. Periodontal health should be assessed during the clinical assessment of HFE-HH patients.

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Significance of Hereditary Hemochromatosis Gene (HFE) Mutations in Chronic Hepatitis C and Hepatocellular Carcinoma Patients in Egypt: A Pilot Study.

Background:Hereditary hemochromatosis is a genetic disease defined by enhanced overloading of iron and associated with Chronic Hepatitis C (CHC). This study aims to evaluate the correlation of the HFE gene mutations on Egyptian CHC with liver disease progression and the risk of HCC development. Methods:The HFE mutations (C282Y and H63D) were genotyped on 100 CHC patients and 50 healthy individuals by a hybridization assay. The serum iron content was also measured for all subjects. Results:A significant elevation of the serum iron, ferritin, and TIBC in HCV-infected patients (p≤0.05). The H63D mutation was detected in 23% of the all studied samples. The serum iron and the H63D heterozygosity were correlated significantly between non-cirrhotic and cirrhotic without HCC patients. Conclusion:The H63D heterozygosity might have a potential role in iron accumulation. Moreover, HFE mutations did not tend to be associated with an increased risk of HCC in cirrhotic patients.

The Role of the Trabecular Bone Score in the Assessment of Osteoarticular Disorders in Patients with HFE-Hemochromatosis: A Single-Center Study from Poland.

Type 1 hereditary hemochromatosis (HH) is an autosomal, recessive genetic entity with systemic iron overload. Iron homeostasis disorders develop as a result of HFE gene mutations, which are associated with hepcidin arthropathy or osteoporosis and may cause permanent disability in HH patients despite a properly conducted treatment with phlebotomies. In this study, selected parameters of calcium and phosphate metabolism were analyzed in combination with the assessment of bone mineral density (BMD) disorders in patients from northern Poland with clinically overt HFE-HH. BMD was determined by a dual-energy X-ray absorptiometry (DXA) test with the use of the trabecular bone score (TBS) function. The study included 29 HH patients (mean age = 53.14 years) who were compared with 20 healthy volunteers. A significantly lower TBS parameter and serum 25-OH-D3 concentration, a higher concentration of intact parathormone and more a frequent occurrence of joint pain were found in HH patients compared with the control group. In HH patients, the diagnosis of liver cirrhosis was associated with lower serum 25-OH-D3 and osteocalcin concentrations. In HH, DXA with the TBS option is a valuable tool in the early assessment of the bone microarchitecture and fracture risk. A supplementation of vitamin D, monitoring its concentration, should be considered especially in HH patients with liver damage and liver cirrhosis.

From the Editor’s Desk…

From the Editor’s Desk…

Whole-body R2∗ mapping to quantify tissue iron in iron storage organs: reference values and a genotype

To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage. Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3±12.2 years) without clinical evidence of an iron storage disease at 1.5 T. R2∗ values were assessed for liver, spleen, pancreas, heart, bones, and brain parenchyma. The HFE genotype was determined regarding the single nucleotide polymorphisms (SNPs) rs74315324, rs1799945, rs41303501, rs1800562, rs1800730. R2∗ values were compared among participants without and with at least one mutation. R2∗ reference values were defined using volunteers without any mutation. Three hundred and one participants had no mutations in any HFE SNP, 182 had at least one mutation. HFE gene mutations were distributed as (heterozygous/homozygous) rs1799945:132/9, rs1800562:33/1, and rs1800730:11/0. Mean R2∗ values±SD (per second) in the group without mutation were: liver: 33.4±12.7, spleen: 24.1±13.8, pancreas: 27.2±6.6, heart: 32.7±11.8, bone: 69.3±21.0, brain parenchyma: 13.9±1.2. No significant difference in R2∗ values were found between participants with and without the HFE gene mutation for any examined iron storage organ (pliver=0.09, pspleen=0.36, ppancreas=0.08, pheart=0.36, pbone=0.98, pbrain=0.74). Reference values of R2∗ in iron storage organs are feasible to support the diagnosis of iron storage diseases. Non-specific mutations in HFE SNPs appear not to affect the phenotype of tissue iron accumulation.

Prevalence of H63D and C282Y Mutations in Hereditary Hemochromatosis (HFE) Gene in Tripoli Region of Libya

Background and Aims: Hereditary hemochromatosis (HH) is an autosomal recessive disorder, characterized by increased intestinal absorption of iron. Excessive amount of iron accumulates in the liver, pancreas, and heart, etc., and eventually leading to organ failure due to iron toxicity and death if untreated. The most common causes of HH are the C282Y and H63D mutations in HFE gene. This study aimed to identify the prevalence of H63D and C282Y alleles among the Libyan population in Tripoli region and to compare the results with other published data. Materials and Methods: This study included 300 randomly selected unrelated Libyan male blood donors, aged between 18 and 50 years. In-house hydrolysis probe real-time polymerase chain reaction and high-resolution melting analysis protocols were developed and employed as screening tools for H63D and C282Y genotyping, respectively, and direct DNA sequencing was used to confirm the results. Results: Seven subjects (2.33%) were detected as homozygous H63D mutation and 72 (24%) were detected as heterozygous, and only one subject was detected as a heterozygous C282Y mutant (0.33%) and no homozygous C282Y mutation was detected. Conclusion: In Libyans residing in Tripoli region, the allele frequency of C282Y was very rare and allele frequency of H63D was common.