hereditary hemochromatosis

Bone scintigraphy is recognized as a noninvasive alternative to endomyocardial biopsy for the diagnostic of wild-type (wATTR) and hereditary ATTR amyloidosis (hATTR). Light chain amyloidosis (AL), Randall-type monoclonal immunoglobulin deposition disease, sarcoidosis, hemochromatosis, Fabry disease, and mucopolysaccharidoses are differential diagnosis of ATTR amyloidosis. Bone scintigraphy allows visualization of extracardiac involvements of AL amyloidosis: pleural, retroperitoneal, liver, spleen, and soft tissue...

IMPORTANCE: HFE gene-associated hereditary hemochromatosis type 1 (HH1) is underdiagnosed, resulting in missed opportunities for preventing morbidity and mortality. OBJECTIVE: To assess whether screening for p.Cys282Tyr homozygosity is associated with recognition and management of asymptomatic iron overload. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study obtained data from the Geisinger MyCode Community Health Initiative, a biobank of biological samples and linked electronic health record data from a rural, integrated health care system...

PURPOSE: Hereditary hemochromatosis (HH) may cause iron deposition in cardiac tissue. We aimed to describe the echocardiographic findings in patients with HH and identify risk factors for cardiac dysfunction. METHODS: In this retrospective study, we included patients with HH who underwent transthoracic echocardiography at our tertiary care center between August 2000 and July 2022. We defined three primary outcomes for cardiac dysfunction: 1) left ventricular ejection fraction (LVEF) < 55%, 2) ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') > 15, and 3) global longitudinal strain (GLS) < 18...

A 55-year-old male, with a strong family history of hereditary hemochromatosis, presented with progressively worsening right-sided tremor and Parkinsonian symptoms. He was diagnosed with hereditary hemochromatosis based on genetic testing and started undergoing regular phlebotomies to reduce his blood iron levels. Despite extensive trials of different pharmaceutical therapies, including levodopa-carbidopa, his Parkinsonian symptoms were not relieved and continued to worsen. This report serves to highlight the importance of early disease identification and intervention in patients with hereditary hemochromatosis to prevent the development of neurological sequelae, as well as a need for further research into effective therapies in such patients...

Hereditary hemochromatosis (HH) is an inherited disorder in which organ damage and other clinical manifestations are commonly seen in patients with a homozygous mutation involving C282Y of the HFE gene, causing increased iron absorption in the intestine. The liver is the primary site of iron deposition, and excessive iron overload can eventually lead to hepatic cirrhosis. Patients who drink significant amounts of alcohol are more likely to develop cirrhosis, and in females, it is commonly seen after menopause...

PURPOSE/OBJECTIVE(S): In the US, incidence rates of hepatocellular carcinoma (HCC) have more than tripled and death rates have doubled since 1980. In 2022, it is expected for 41,260 new cases to be diagnosed with 30,520 deaths. Many etiologies contribute to the development of HCC including alcoholic cirrhosis, cryptogenic cirrhosis, HCV, HBV, NASH, and genetic disorders like hereditary hemochromatosis. An increasing number of patients are not candidates for curative options such as resection or transplant and the role of alternative liver directed as therapies has increased...

The peptide hormone hepcidin is central to the regulation of iron metabolism, influencing the movement of iron into the circulation and determining total body iron stores. Its effect on a cellular level involves binding ferroportin, the main iron export protein, preventing iron egress and leading to iron sequestration within ferroportin-expressing cells. Hepcidin expression is enhanced by iron loading and inflammation and suppressed by erythropoietic stimulation. Aberrantly increased hepcidin leads to systemic iron deficiency and/or iron restricted erythropoiesis as occurs in anemia of chronic inflammation...

An annual physical examination within a primary care setting, including evaluation of liver enzymes and abnormal serology, is incidental and often asymptomatic. Fatty liver is the most common etiology for transaminitis. Hepatobiliary imaging studies, viral hepatitis serology, evaluation of metabolic liver disease, and alcohol consumption history should be performed for transaminitis evaluation. In patients with prior history of excessive alcohol consumption, transaminitis is often assumed to be alcohol-related...

Hereditary hemochromatosis (HH) is an autosomal recessive bleeding disorder characterized by tissue overload of iron. Clinical systemic manifestations in HH include liver disease, cardiomyopathy, skin pigmentation, diabetes mellitus, erectile dysfunction, hypothyroidism, and arthropathy. Arthropathy with joint pain is frequently reported at diagnosis and mainly involves the metacarpophalangeal and ankle joints, and more rarely, the hip and knee. Symptoms in ankle joints are in most cases non-specific, and they can range from pain and swelling of the ankle to deformities and joint destruction...

Iron overload disorders can present as non-specific symptoms and develop gradually but, if untreated, can be very fatal. The common causes include multiple blood transfusions for chronic anemia and increased iron absorption, including hereditary hemochromatosis (HH). HH is one of the common causes of iron overload disorders and usually presents with liver cirrhosis in a setting of significantly elevated ferritin and elevated transferrin saturation. Alcoholic hepatitis is a clinical syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol...

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE , the gene associated with autosomal recessive inheritance hereditary hemochromatosis...

Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis...

Hereditary hemochromatosis is an autosomal recessive condition with incomplete penetrance that is most commonly caused by a mutation in the HFE gene. Hereditary hemochromatosis can remain asymptomatic in some patients until triggered by certain events. Porphyria cutanea tarda is a condition that can lead to iron overload due to defective synthesis of heme and can cause the onset of adult-onset hereditary hemochromatosis. Herein, we present a case where a 77-year-old man presented with painful blisters on the sun-exposed areas of his hands and was diagnosed with porphyria cutanea tarda...

BACKGROUND: Hereditary hemochromatosis (HH) is a genetic disease that leads to increased iron accumulation in several organs. Cardiomyocytes are highly susceptible to this damage owing to their high iron uptake, and cardiovascular complications account for 1/3 of the deaths in the natural course of HH. Additionally, excess iron intake and associated oxidative stress may accelerate the aging of the cardiovascular system, regardless of the age of patients with HH. We aimed to investigate the role of standard and speckle-tracking echocardiography (STE) in revealing heart differences in patients with HH considering the disease stage and the patient age...

In a previous report, a 39-year-old patient with high serum iron levels from hereditary hemochromatosis (HH) was diagnosed with a form of retinal degeneration called bull's eye maculopathy. This is atypical for patients with HH, so it was theorized that the low serum levels of ferroxidase ceruloplasmin (CP) of this patient coupled with the high iron levels led to the retinal degeneration. CP, by oxidizing iron from its ferrous to ferric form, helps prevent the oxidative damage caused by ferrous iron. To test this, a hepcidin knockout (KO) mouse model of HH was combined with Cp KO to test whether the combination would lead to more severe retinal degeneration...

Hyperferritinemia is a common reason for referral to a hepatogastroenterologist. The most frequent causes are not associated with iron overload (e.g. inflammatory diseases, alcohol abuse, metabolic syndrome, etc.). However, hyperferritinemia can also be caused by a genetic variant in one of the iron regulatory genes, called hereditary hemochromatosis, often but not always associated with iron overload. A variation in the human Hemostatic Iron Regulator protein (HFE) gene is the most common genotype, but many other variants have been described...

Iron overload is a condition involving excessive iron deposit in various organs, the liver being the main target organ for iron deposition and overload which are associated with significant liver morbidity and mortality. Iron overload can be categorized into primary and secondary causes. Primary iron overload, so-called hereditary hemochromatosis, is a well-recognized disease with available standard treatment recommendations. However, secondary iron overload is a more diverse disease with many unclear areas to be explored...

Hereditary hemochromatosis type 4 is an autosomal-dominant inherited disease characterized by a mutation in the SLC40A1 gene encoding ferroportin. This condition can be further subdivided into types 4A (loss-of-function mutations) and 4B (gain-of-function mutations). To date, only a few cases of type 4B cases have been reported, and the treatment has not been clearly mentioned. Here, we report a genotype of hereditary hemochromatosis type 4B involving the heterozygous mutation c.997 T > C (p...

Wilson's disease and HFE-hemochromatosis are autosomal-recessively inherited metabolic diseases of the liver. Copper overload in case of Wilson's disease and iron overload in case of hemochromatosis lead to organ damage of the liver and other organs. In order to diagnose these diseases at an early stage and introduce therapy, knowledge of the symptoms and diagnostic criteria of these diseases is important. Iron overload in hemochromatosis patients is treated with phlebotomies and copper overload in Wilson's disease patients with either chelating medications (D-penicillamine or trientine) or zinc salts...

Three histologic patterns of gastric siderosis (GS) are described: pattern A (predominantly in lamina propria stromal cells-gastric lamina propria siderosis [GLPS]), pattern B (mostly extracellular crystalline iron) and pattern C (predominantly in glandular epithelium-gastric glandular siderosis [GGS]). This study aimed to analyze the association of GGS with clinicopathologic features using 3 cohorts. Cohort #1 consisted of 76 gastric siderosis cases. Upon classifying the cases into 3 groups by percentage of glandular involvement (negative, 1% to 5%, ≥5% GGS), the degree of GGS was positively associated with serum ferritin levels (P=0...