Moderate to severe liver siderosis and raised AST are independent risk factors for vitamin D insufficiency in ß-thalassemia patients.

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with ß-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with ß-thalassemia. In this multicenter and observational study, all ß-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5-46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38-3.89 and 2.62, 95% CI 1.43-4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54-0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.

HFE genotyping in patients with elevated serum iron indices and liver diseases.

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 µg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population.

[Arc welder's lung]. / Pulmón del soldador de arco.

Pneumoconiosis of electric arc welder or siderotic pneumoconiosis was described by Doig and McLaughlin in 1936 as a lung disease caused by chronic inhalation of iron fumes in electric arc welders. We present a case report of electric arc welder siderosis associated with high levels of ferritin, without findings of iron deposit in any other organ.

Pulmón del soldador de arco / Arc welder's lung

La siderosis del soldador o neumoconiosis siderótica fue descripta por Doig y McLaughlin en 1936 como una enfermedad pulmonar causada por la inhalación crónica de polvo de hierro en soldadores de arco eléctrico. Presentamos un caso de siderosis del soldador asociada a aumento de los niveles de ferritina, sin hallazgo de depósito de hierro en otros órganos y sin causas evidentes de hemosiderosis secundaria.

Pneumoconiosis of electric arc welder or siderotic pneumoconiosis was described by Doig and McLaughlin in 1936 as a lung disease caused by chronic inhalation of iron fumes in electric arc welders. We present a case report of electric arc welder siderosis associated with high levels of ferritin, without findings of iron deposit in any other organ.

Total body iron overload in welder's siderosis.

Welder's siderosis occurs as a consequence of the inhalation of iron dust. The iron overload of welder's siderosis is usually considered to be confined to the lungs. Here we present three proven cases of welder's siderosis associated with evidence of increased total systemic iron stores, as evidenced by increased serum ferritin levels. Multiple investigations including molecular genotyping for the common mutations found in genetic haemochromatosis failed to prove this was due to haemochromatosis, nor was there any evidence of any other recognised cause of systemic iron overload. Thus the systemic iron overload described seems likely to be due to either occupational exposure, an uncharacterised genetic haemochromatosis, or a combination of both.

Elevated CSF lactoferrin in superficial siderosis of the central nervous system.

This study sought to identify abnormalities in the levels of iron transport proteins in patients with superficial siderosis of the central nervous system. We compared patients with superficial siderosis (n = 7) with patients suffering from various other neurological disorders (n = 176, total). CSF and serum levels of lactoferrin, and CSF levels of transferrin were measured by enzyme-linked immunosorbent assay. Serum transferrin was measured by nephelometry. Lactoferrin, but not transferrin, levels in the CSF were significantly elevated in superficial siderosis. Unexpectedly, CSF transferrin was decreased in multiple sclerosis patients. Enhanced CSF lactoferrin may reflect an increased iron transport requirement in the central nervous system in superficial siderosis and might be a useful measure for monitoring response to therapy.

Serum transferrin receptor in hereditary hemochromatosis and African siderosis.

The present investigation evaluated the serum transferrin receptor concentration in subjects with nontransfusional iron overload who were identified in two separate studies on the basis of a serum ferritin level above 400 micrograms/L. Subjects with preclinical hereditary hemochromatosis were evaluated in the first study and those with the African form of iron overload in the second. In the first study, hereditary hemochromatosis was identified in 14 white men on the basis of a persistent elevation in transferrin saturation above 55%. The serum receptor concentration was elevated above the upper cut-off of 8.5 mg/L in two of the subjects, but the mean receptor of 6.1 +/- 1.4 mg/L (mean +/- 2 SE) did not differ significantly from the normal mean for this assay of 5.6 +/- 0.3 mg/L. In the same study, 60 control subjects with secondary iron overload were identified on the basis of a serum ferritin persistently above 400 micrograms/L, with a normal serum C-reactive protein concentration but with a transferrin saturation < 55%. Three of these subjects had an elevated serum receptor concentration but the mean value of 5.5 +/- 0.4 mg/L did not differ from normals nor from subjects with hemochromatosis. In the second study, 49 black Africans with iron overload were divided into those with or without an elevated transferrin saturation. The mean serum receptor concentration of 5.0 +/- 0.8 mg/L and 4.5 +/- 0.4 mg/L, respectively, did not differ statistically. It was concluded that there is no evidence of generalized dysregulation of the transferrin receptor in hemochromatosis or African siderosis.

Superficial siderosis of the central nervous system: report of three cases and review of the literature.

We present 3 cases and a review of the literature to demonstrate the current state of clinical diagnosis and therapy of superficial siderosis of the central nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent xanthochromia of the cerebrospinal fluid and confirmed by the presence of erythrophages, siderophages and iron-containing pigments. Deposition of free iron and hemosiderin in pial and subpial structures leads to intoxication of the central nervous system and represents the pathophysiological mechanism of superficial siderosis. Hypointensity of the marginal zones of the central nervous system on T2 weighted MR images indicates an iron-induced susceptibility effect and seems pathognomonic for superficial siderosis. In 39 of the 43 previously described cases superficial siderosis was verified by biopsy or autopsy. Today magnetic resonance imaging enables diagnosis at an early stage of the disease. Therapeutic management requires the elimination of any potential source of bleeding. In patients with unknown etiology no proofed therapy is yet available.

[Prevalence, causes and effects of increased iron storage in patients with kidney transplantation]. / Prävalenz, Ursachen und Folgen einer vermehrten Eisenspeicherung bei Nierentransplantierten.

Patients on chronic hemodialysis often need blood transfusions due to erythropoietin deficiency. Even after successful kidney transplantation iron overload may persist. Former histological studies have revealed siderosis of the liver in 69% of all patients whose serum ferritin was above 1100 ng/ml. The aim of the present study was to evaluate the influence of iron overload on liver function. In 146 symptom free patients with renal allografts serum ferritin was determined to detect possible iron overload. Serum ferritin between 4 and 5480 ng/ml were found (women: 358.7 +/- 105.3; men 282.4 +/- 63.3 ng/ml; x +/- SEM). Twelve patients (8.1%) had ferritin levels higher than 1100 ng/ml. These twelve patients as well as another group of eight patients with renal allografts whose serum ferritin was known to be higher than 1100 ng/ml were included for further evaluation. Their data were matched and compared with those of a control group also patients with renal allograft (same age and sex) whose serum ferritin was lower than 1100 ng/ml. Transaminases (SGPT 22.6 +/- 3.6 vs. 15.4 +/- 6.0 U/l; SGOT 14.7 +/- 2.0 vs. 13.0 +/- 4.8 U/l) and plasma glucose (90.5 +/- 7.1 vs. 76.8 +/- 3.7 mg/dl) were found to be significantly higher (p less than 0.05) in patients with serum ferritin levels above 1100 ng/ml. Elevated transaminases were significantly more frequent in patients with high serum ferritin (9 vs. 2; p less than 0.02) as compared with the control. Ferritin levels significantly correlated with the number of preceding blood transfusions (p less than 0.002). Hbs-persistence was detected in six out of 20 patients with high ferritin levels but only in one out of 20 in the control group (p less than 0.05) whereas anti-Hbs prevalence was not different in the two groups. These data indicate that chronic iron overload should be considered as a possible cause of chronic liver disease in patients with renal allografts.

[Disturbances in iron utilization in acute leukemia and preleukemia]. / Eisenverwertungsstörungen bei akuter Leukämie und Präleukämie.

With Prussian blue reaction nonhaemoglobin iron in the erythroblasts is demonstrable. Three pathological sideroblast types are recorded separately: abnormal intermediate type I and II sideroblasts and ring sideroblasts, representing increasing levels of sideroachrestic disturbance. This permits the classification of sideroachrestic disturbances into four degrees of seriousness. The frequency of a sideroachrestic disturbance in 47 untreated patients with acute myeloid leukaemia was 87%. Among 11 patients with preleukaemic condition, 8 had a disturbance of iron utilisation. In both preleukaemia and leukaemia mainly intermediate sideroblasts were present. All patients with preleukaemia developed leukaemia within 1-20 months. In the course of preleukaemic condition a slight increase of iron misutilisation was obvious when terminating in overt leukaemia. This could be of prognostic importance. After treatment, pathological sideroblasts disappeared only in 2 out of 15 patients with complete remission. There was no correlation between effect of therapy and course of iron misutilisation.

[Serum ferritin in iron overload]. / Serumferritin bei Eisenüberladung.

Even with uncomplicated iron overload, serum ferritin which can be identified in the circulating blood by sensitive immunochemical methods has a direct and quantitative correlation to the iron stored in the organism. The relation of stored iron and serum ferritin is not linear, but has an exponential character. The diagnostic function of serum ferritin as an indicator of stored iron, however, is virtually not influenced by it. The indications listed in Tab. 3 can be demarcated for diagnostic application in cases of iron overload. Hitherto, the molecular microheterogenicity of serum ferritin has exercised no essential impact on its diagnostic application. High ferritin concentrations may arise in the circulating blood by a number of disease processes listed in Tab. 4, without the simultaneous existence of a respective iron overload of the tissue. These correlations have to be observed in the diagnostic application of determining serum ferritin as well as in methodical possibilities of fault (high dose hook effect), thus limiting the use of serum ferritin as an indicator of stored iron both in case of iron overload and iron deficiency. As in all isolated laboratory investigations, all other clinical and chemical laboratory information available about the individual patient has to be taken into account in each case for interpreting the serum ferritin concentration.

Host-associated iron transfer factor in normal humans and patients with transfusion siderosis.

A low molecular weight iron-binding substance that promotes bacterial growth in vitro by increasing iron availability was identified in human blood and urine. Partial purification and physical characterization indicate that this factor is similar to the host-associated iron transfer factor (HAITF) previously isolated from mammalian tissue. HAITF was found to be significantly elevated in the blood of patients with thalassemia who have transfusional siderosis. The level of HAITF in the blood of these patients was also found to correlate with that of serum iron and serum glutamic-oxaloacetic transaminase (SGOT) but not with that of serum ferritin. Thus, elevated blood levels of HAITF may explain the increased susceptibility to infection seen in patients with iron overload. Its physiologic role, however, may involve the transport of iron within cells.

Monocyte ferritin in idiopathic haemochromatosis, thalassaemia and liver disease.

Monocyte ferritin (MF) content was measured in normal subjects and patients with a variety of disorders of iron storage. MF was above the normal range in 4 patients with idiopathic haemochromatosis (IHC). However, in 4 patients with transfusion siderosis (TS), secondary to aplastic anaemia, who had similar elevations in serum ferritin, MF was highly elevated. 10 patients with thalassaemia intermedia and thalassaemia major with no previous history of transfusions, but with elevated serum ferritin, also had significantly elevated MF. Disproportionately low MF in IHC could reflect defective ferritin metabolism in reticuloendothelial cells in this disorder. Finally, in 3 patients with acute rises in serum ferritin caused by acute hepatitis, MF was not increased. This suggests that MF is not directly affected by high circulating levels of serum ferritin raised acutely, but rather reflects iron storage status in conditions not associated with primary disorders of iron metabolism.