Negative correlation between erythrocyte count and mean corpuscular volume or mean corpuscular haemoglobin in diabetic and non-diabetic subjects

Negative correlation was observed between erythrocyte count (RBC) and mean corpuscular volume (MCV) or mean corpuscular haemoglobin (MCH) in both sexes of diabetic and non-diabetic Libyans. The slopes of regression lines for MCV-RBC and MCH-RBC of diabetic patients were significantly lower (P less than 0.001) than those of their non-diabetic counterparts. Positive correlation was found between MCH and MCV. The slope of the regression line for MCH-MCV of diabetic patients was not significantly different from that of non-diabetic subjects.     

Effect of triploidy on turbot haematology

This study was carried out to compare key haematological features of diploid (2n) and triploid (3n) turbot as a first step towards the assessment of the ability of 3n turbot to withstand sub-optimal culture conditions. Morphometric indices of erythrocytes were determined on blood smears by light microscopy. Triploidy significantly (P<0.001) increased all morphometric indices measured in the erythrocytes, including size, surface, and volume, except for the size of minor nuclear axis. The increase in cell size was larger for the major (31.0%) than for the minor (8.3%) axis, thus rendering erythrocytes of 3n turbot more ellipsoidal. The increase in erythrocyte volume (45.9%) was close to the theoretical expected 50% increase as a result of one extra chromosome set. Haematological indices were measured automatically by a haematological Coulter Counter. Triploid turbot had lower numbers of red blood cells (RBC: 1.84 cells pL(-1) in 2n vs. 1.27 cells pL(-1) in 3n; P<0.001) but they were of a larger size (Mean corpuscular volume [MCV]: 145.51 fL in 2n vs. 181.78 fL in 3n; P<0.001). However, the decrease in RBC was not compensated by the increase in MCV, and thus, triploidy decreased the haematocrit (Hct: 26.80% in 2n vs. 23.11% in 3n; P<0.001) and total blood haemoglobin concentration (Hb: 73.74 g l(-1) in 2n vs. 67.54 g l(-1) in 3n; P<0.05). In contrast, mean corpuscular hemoglobin (MCH: 40.27 pg in 2n vs. 53.28 pg in 3n; P<0.001) was higher for 3n turbot as a result of their larger erythrocytes although MCH concentration (MCHC: 0.28 pg fL(-1) in 2n vs. 0.29 pg fL(-1) in 3n did not significantly differ. RBC, Hct and MCV were also determined manually using light microscopy. In general, discrepancies between the two methods were small (overall approximately 7%) but the Coulter Counter tended to overestimate RBC and Hct (and thus to underestimate MCV). Nevertheless, relative differences between ploidies were very similar, thus verifying triploidy-associated changes in hematological features. These changes, as determined in the present study, are essential when evaluating the feasibility of triploid turbot for intensive aquaculture systems in which unfavorable situations may occur.     

Serum ferritin and transferrin saturation levels in β⁰ and β(+) thalassemia patients

There have been few studies on the mutations that cause heterozygous beta-thalassemia and how they affect the iron profile. One hundred and thirty-eight individuals were analyzed, 90 thalasemic β? and 48 thalasemic β(+), identified by classical and molecular methods. Mutations in the hemochromatosis (HFE) gene, detected using PCR-RFLP, were found in 30.4% of these beta-thalassemic patients; heterozygosity for H63D (20.3%) was the most frequent. Ferritin levels and transferrin saturation were similar in beta-thalassemics with and without mutations in the HFE gene. Ferritin concentrations were significantly higher in men and in individuals over 40 years of age. Transferrin saturation also was significantly higher in men, but only in those without HFE gene mutations. There was no significant difference in the iron profile among the β? and β(+) thalassemics, with and without HFE gene mutations. The frequency of ferritin values above 200 ng/mL in women and 300 ng/mL in men was also similar in β? and β(+) thalassemics (P > 0.72). Our conclusion is that ferritin levels are variable in the beta-thalassemia, trait regardless of the type of beta-globin mutation. Furthermore, HFE gene polymorphisms do not change the iron profile in these individuals.     

A two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes

Backgrounds

We compared the usefulness of fasting plasma glucose (FPG), or hemoglobin A1c (HbA1c), or both in predicting type 2 diabetes.

Methods

This retrospective cohort study investigated 9,322 Japanese adults (4,786 men and 4,536 women), aged 19–69 yrs, free of diabetes at baseline. Usefulness was assessed by predictive values (PV), sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) maximised under the best cut-off point.

Results

During the average 6 years of follow-up, 221 men (4.6%) and 92 women (2%) developed diabetes. The best cut-off points for FPG (i.e., 5.67 mmol/l for men and 5.5 mmol/l for women) gave excellent AUROC, and the highest positive PV (13% for men and 9% for women) in predicting diabetes. In high risk subjects with FPG 6.1–6.9 mmol/l, 119 men (26.8%) and 39 women (28.3%) developed diabetes. Under the best cut-off points of FPG 6.39 mmol/l and A1c 5.8, AUROC and positive PV for FPG slightly decreased indicating FPG became less useful and were statistically indistinguishable from those for HbA1c in men. In fact, HbA1c was the most useful in women: HbA1c of 6.0% gave the highest positive likelihood ratio of 2.74 and larger AUROC than did FPG. Although AUROC for HbA1c was acceptable and indistinguishable from that for the combined use, HbA1c had higher specificity and positive LR than did the combined use.

Conclusions

This study demonstrated that FPG was the most useful to predict diabetes in the general population. However, in subjects with FPG 6.1–6.9 mmol/l, FPG became less useful and diagnostic performance of FPG was indistinguishable from that of HbA1c in men whereas HbA1c was the most useful in women. Thus, a two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.     

A primer for predicting risk of disease in HFE-linked hemochromatosis

Since the discovery of the hemochromatosis gene (HFE) in 1996, there has been increasing interest in diagnostic testing for the C282Y and H63D mutations. The high frequency of these two alleles and their incomplete penetrance in homozygotes and compound heterozygotes make genetic counseling for hemochromatosis different from some other autosomal recessive conditions in that parents and children may also be at risk for iron overload, while homozygotes may remain asymptomatic. We provide a guideline for genetic counseling in HFE-linked hemochromatosis based on the genetic probability of inheriting HFE mutations and known information about expression of iron overload in various HFE genotypes. Genetic probabilities were based on allele frequencies derived from large population studies and Hardy-Weinberg equilibrium estimates. Expression of iron overload in those of various genotypes was based on available estimates of serum ferritin from population screening studies. Estimates for the likelihood of clinical iron overload requiring follow-up screening or treatment are provided by gender and genotype. The probability of inheriting HFE mutations and developing iron overload can be estimated in family members of a proband with HFE mutations. Many C282Y homozygotes will not have clinical iron overload. The risk is highest in men and their C282Y homozygous brothers and significantly lower in homozygous women. Iron overload is uncommon in compound heterozygotes and H63D homozygotes.     

Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in whites and blacks in the Hemochromatosis and Iron Overload Screening Study

We compared initial screening data of 44,082 white and 27,124 black Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. Each underwent serum transferrin saturation (TfSat) and ferritin (SF) measurements without regard to fasting, and HFE C282Y and H63D genotyping. Elevated measurements were defined as: TfSat more than 50% (men), more than 45% (women); and SF more than 300 ng/ml (men), more than 200 ng/ml (women). Mean TfSat and percentages of participants with elevated TfSat were significantly greater in whites than in blacks. Mean SF and percentages of participants with elevated SF were significantly greater in blacks than in whites. TfSat and SF varied by gender and age in whites and blacks. Prevalences of genotypes that included either C282Y or H63D were significantly greater in whites than in blacks. The prevalence of elevated TfSat and SF plus genotypes C282Y/C282Y, C282Y/H63D, or H63D/H63D was 0.006 in whites and 0.0003 in blacks. Among whites with HFE C282Y homozygosity, 76.8% of men and 46.9% of women had elevated TfSat and SF values. Three black participants had HFE C282Y homozygosity; one had elevated TfSat and SF values. Possible explanations for differences in TfSat and SF in whites and blacks and pertinence to the detection of hemochromatosis, iron overload, and other disorders with similar phenotypes are discussed.     

Transferrin saturation phenotype and HFE genotype screening for hemochromatosis and primary iron overload: predictions from a model based on national, racial, and ethnic group composition in central Alabama

There is interest in general population screening for hemochromatosis and other primary iron overload disorders, although not all persons are at equal risk. We developed a model to estimate the numbers of persons in national, racial, or ethnic population subgroups in Jefferson County, Alabama, who would be detected using transferrin saturation (phenotype) or HFE mutation analysis (genotype) screening. Approximately 62% are Caucasians, 37% are African Americans, and the remainder are Hispanics, Asians, or Native Americans. The predicted phenotype frequencies are greatest in a Caucasian subgroup, ethnicity unspecified, which consists predominantly of persons of Scotch and Irish descent (0.0065 men, 0.0046 women), and in African Americans (0.0089 men, 0.0085 women). Frequencies of the HFE genotype C282Y/C282Y > or = 0.0001 are predicted to occur only among Caucasians; the greatest frequency (0.0080) was predicted to occur in the ethnicity-unspecified Caucasian population. C282Y/C282Y frequency estimates were lower in Italian, Greek, and Jewish subgroups. There is excellent agreement in the numbers of the ethnicity-unspecified Caucasians who would be detected using phenotype and genotype criteria. Our model also indicates that phenotyping would identify more persons with primary iron overload than would genotyping in our Italian Caucasian, Hispanic, and African American subgroups. This is consistent with previous observations that indicate that primary iron overload disorders in persons of southern Italian descent and African Americans are largely attributable to non-HFE alleles. Because the proportions of population subgroups and their genetic constitution may differ significantly in other geographic regions, we suggest that models similar to the present one be constructed to predict optimal screening strategies for primary iron overload disorders.     

HFE genotype frequencies in consecutive reference laboratory specimens: comparisons among referral sources and association with initial diagnosis

We quantified HFE genotype frequencies in specimens submitted by physicians grouped by specialty and determined associations of genotypes with initial diagnosis based on phenotyping in patients evaluated at an iron disorders center. Of 526 specimens (519 from Alabama), these "typical" hemochromatosis-associated genotypes were detected: 85 C282Y/C282Y, 50 C282Y/H63D, and 27 H63D/H63D. Respective frequencies of C282Y/C282Y in specimens from an iron disorders center (n = 156), gastroenterologists (n = 147), hematologists/medical oncologists (n = 85), liver transplant surgeons (n = 11), endocrinologists and rheumatologists (n = 9), and "other sources" (n = 7) were greater (p < 0.05) than in population controls. In 44 patients from an iron disorders center initially diagnosed as "presumed hemochromatosis," 27 (61.4%) had C282Y/C282Y, 10 (22.7%) had C282Y/H63D, and 3 (6.8%) had H63D/H63D. C282Y/C282Y was not detected in 48 patients with "abnormality probably not an iron overload disorder." A total of 20.5% of 44 family members of patients had "typical" hemochromatosis-associated HFE genotypes (7.0% controls; p = 0.02). We conclude that most physicians who submitted specimens identify patients by phenotyping who have greater frequencies of "typical" hemochromatosis-associated HFE genotypes than controls, and that HFE mutation testing is useful in detecting hemochromatosis in family members of persons with hemochromatosis or iron overload.     

Clinical significance of a high mean corpuscular volume in nonanemic patients.

A prospective study of the clinical significance of macrocytosis (mean corpuscular volume 100 fL or more) was carried out for 9 months in a teaching hospital in 1975. Of the 140 patients with macrocytosis at the time of admission (0l7% of all hospital admissions) 46 (33%) had low activity of serum or erythrocyte folate, or both, and 16 (11%) had low serum vitamin B12 concentrations. Among the 78 patients with normal B12 and folate values the most commonly associated significant clinical conditions were alcoholism or hepatic disease (36 patients), malignant disease or the effects of chemotherapy (25 patients) and chronic obstructive lung disease (10 patients).     

Age‐related changes in mean corpuscular volumes in patients without anaemia: An analysis of large‐volume data from a single institute

Although the mean corpuscular volume (MCV) has been associated with various diseases, these associations in relation to the age‐related trends in MCV remain unclear. Therefore, we used a dataset with over one million values to identify the relationship between ageing and MCV changes. All laboratory data obtained between November 1998 and November 2019 at Chungbuk National University Hospital were retrospectively collected. After excluding cases with missing values for individual complete blood count parameters, outlier MCV values, and ages less than 1 year and more than 88 years, 977,335 MCV values were obtained from 309,393 patients. Principal component analysis of blood components with ages and analysis of the median value changes for each blood component across decade‐wise age groups were conducted to identify relationships between ageing and changes in blood components. The median values of MCV showed gradual increments with age. The linear relationship for patients aged 1–25 years had a larger slope than that for patients aged 26–88 years. For MCV, the equation for patients aged 1–25 years was 0.40*(age) + 81.24 in females and 0.45*(age) + 79.58 in males. The equation for patients aged 26–90 years was 0.04*(age) + 88.97 in females and 0.06*age + 88.30 in males. Among patients aged >40 years, the MCV value was higher in men than in women. Analysis of a large dataset showed that the MCV gradually increased with age and the linear relationship differed between patients aged 1–25 and 26–88 years.     

Increased urinary excretion of 8-iso-prostaglandin F2alpha in patients with HFE-related hemochromatosis: a case-control study

The hypothesis according to which iron overload could be harmful has been extensively and controversially discussed in the literature. One underlying pathological mechanism may be elevated oxidative stress. Thus, we studied the correlation between hemochromatosis and an established marker of oxidative stress, 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha, iPF2alpha-III, 15-F2t-IsoP). We enrolled 21 patients with hemochromatosis, positive for the homozygous C282Y mutation in the HFE gene, and 21 healthy controls frequency-matched by age and gender in a case-control study design. The objective was to show that iron overload in HFE-related hemochromatosis is associated with increased oxidative stress assessed through 8-iso-PGF(2alpha) urinary excretion, and that oxidative stress is impacted by iron-removal treatment (phlebotomy). Study parameters were transferrin saturation, 8-iso-PGF(2alpha) urine excretion, transferrin, ferritin, serum iron, and vitamins A and E for all participants. Iron concentration in the liver and non-transferrin-bound iron were measured in patients only. We found a significant difference in 8-iso-PGF2alpha in patients (245 [interquartile range 157-348] pg/mg creatinine) compared with controls (128 [106-191] pg/mg creatinine, P = 0.002). Vitamin A was significantly reduced in cases (0.34 [0.25-1.83] microg/ml compared to 3.00 [2.11-3.39] microg/ml, P < 0.001), while vitamin E did not show a significant difference in cases (14.7 [11.5-18.1] microg/ml) compared with controls (14.9 [13.1-19.2] microg/ml, P = 0.52). After phlebotomy treatment and normalization of the iron parameters in the hemochromatosis group, serum vitamin A levels were significantly increased (1.36 [1.08-1.97] microg/ml, P = 0.035 vs. baseline, P < 0.001 vs. controls) and 8-iso-PGF2alpha urinary excretion was lowered to control levels (146 [117-198] pg/mg creatinine, P = 0.38 vs. controls). In our study, HFE-related hemochromatosis was associated with increased oxidative stress and hypovitaminemia A in C282Y homozygotes. The increased oxidative stress was reversible by normalization of the iron load by phlebotomy. Thus, phlebotomy is an effective and adequate means for reducing oxidative stress in these patients.     

The Q283P amino-acid change in HFE leads to structural and functional consequences similar to those described for the mutated 282Y HFE protein

In Caucasians, 4–35% of hemochromatosis patients carry at least one chromosome without a common HFE mutation (i.e. C282Y, H63D and S65C). Several studies have now shown that iron overload phenotypes in such patients can be associated with uncommon HFE mutations. We previously supported implication of the C282Y/Q283P compound heterozygous genotype in hemochromatosis phenotypes and, based on molecular dynamics simulations, proposed that the Q283P substitution prevents normal folding of the HFE ₃-domain. In the current work, we have used HeLa cells carrying wild-type or Q283P-mutant HFE cDNA under the control of a tetracycline-sensitive promoter to functionally characterise the Q283P mutation. Experiments using cells over-expressing wild-type HFE confirm the existence of ₂microglobulin(₂m)/HFE and HFE/transferrin receptor 1 (TfR1) interactions, as well as the capacity of HFE to reduce transferrin-mediated iron uptake. In contrast, neither ₂m/HFE nor HFE/TfR1 complex formation was detected in cells over-expressing the mutated form of HFE. Moreover, the 283P HFE protein was found to have a very limited effect on the major cellular iron uptake pathway. Combined, our results indicate that the Q283P mutation leads to structural and functional consequences similar to those described for the main hereditary hemochromatosis mutation. As a consequence, our study has implications for the screening of hemochromatosis patients that have one or two copies of HFE which lack the main mutations. It also highlights that protein structure prediction methods could be more generally used to better interpret relationships between rare genotypes and molecular diagnosis of a human inherited disorder.     

Mature hematology in neonatal walruses supports diving alongside their mothers

An animal's physiology limits the environmental conditions where it can persist; quantifying the physiology of the walrus is timely since they are being impacted by alterations in sea ice. We examined postnatal changes in hematology, an important attribute that supports diving, by analyzing a longitudinal data set from aquaria walruses (five males and nine females) sampled from 0.04 to 12.0 years of age (n = 795 samples). Red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), and mean corpuscular hemoglobin content (MCHC) did not change markedly after birth and appears to have not been influenced by sex. Estimated values at birth were RBC: 3.78 ± 0.12 × 10⁶ mm⁻³, Hb: 17.62 ± 0.82 g dl⁻¹, Hct: 45.21 ± 2.01%, MCV: 118.99 ± 3.99 fl, MCH: 47.10 ± 1.77 pg, and MCHC: 39.60 ± 0.70 g dl⁻¹. Compared to newborns, there were only subtle decreases in RBC, Hb, and MCHC, and a slight increase in MCV in the years following birth; Hct and MCH appear not to have changed. Unlike other pinnipeds, walruses swim within days of birth and have a prolonged 2-year nursing interval. Mature hematology early in life supports breath-holding, as young walruses must transit under sea ice with patchily distributed breathing holes.     

Maternal serum proinflammatory cytokines in preterm labor with intact membranes: neonatal outcome and histological associations

Our aim was to compare maternal serum concentrations of interleukin(IL)-1alpha IL-1beta, IL-6 and IL-8 in pregnancies complicated by preterm labor (PTL), with the levels in healthy controls at comparable gestational age, and to determine if these assays have any value in the prediction of early-onset neonatal infection or histological chorioamnionitis. The study population consisted of 65 women with new-onset PTL, and 31 healthy controls. Maternal serum concentrations of IL-6 (8.40 versus 3.30 pg/mL; p = 0.002) and IL-1beta (2.20 versus 0.50 pg/mL; p = 0.003) were significantly higher in patients with PTL as compared to healthy pregnant women. The IL-1beta concentration (13.60 versus 1.20 pg/mL; p = 0.02) was significantly higher in the serum of mothers whose babies developed early-onset infections, than in mothers of newborns that were healthy. However, its predictive value, and the value of the other cytokines studied, was poor. In addition, IL-1beta levels (28.79 versus 5.19 pg/mL; p = 0.001) were significantly higher in patients with histological chorionamnionitis, than in those without the condition,. The cut-off value of >or= 14 pg/mL predicted inflammatory changes with a sensitivity of 80%, specificity of 86%, PPV of 80% and NPV of 86%. IL-1beta seems to be of moderate value in the prediction of histological chorioamnionitis.     

Receiver operating characteristic curve analysis of BMI in assessing obesity among adult Bengalee males in India

The present study attempted to understand the appropriateness of different body mass index (BMI) cut-off points in assessing obesity. Four hundred thirty adult Bengalee males with mean age 36.48 +/- 12.23 years (mean +/- SD) from West Bengal, India were studied. Height, weight and percent body fat were measured and BMI was derived following standard equation. Receiver operating characteristic (ROC) curve analysis demonstrated low sensitivity and high specificity of international (> or = 30 kg/m2) and proposed (> or = 25 kg/m2) BMI cut-off points in identifying individuals with obesity. Furthermore, these international and proposed BMI cut-off points also found to be in substantial misclassification to assess obesity as much as 32.09% and 17.44% respectively. However, based on ROC curve analysis, a BMI cut-off point of > or = 24 kg/m2 revealed optimal sensitivity (83.66%) and specificity (90.61%) and as well as less misclassification (11.86%) in assessing obesity among the adult Bengalee males. The present study accentuated that the international and proposed BMI cut-off points so far might not be appropriate in assessing obesity and on the other hand, lower BMI cut-off point (> or = 24 kg/m2) has relatively high sensitivity and specificity in assessing obesity as well. Therefore, the present study envisages the requirement of further lowering down of BMI cut-off point in assessing excess body fat in adult Bengalee males.     

Development of hematological respiratory variables in late chicken embryos: the relative importance of incubation time and embryo mass

Oxygen demand increases during embryonic development, requiring an increase in red blood cells (RBCs) containing hemoglobin (Hb) to transport O(2) between the respiratory organ and systemic tissues. A thorough ontogenetic understanding of the onset and maturation of the complex regulatory processes for RBC concentration ([RBC]), Hb concentration ([Hb]), hematocrit (Hct), mean corpuscular indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration ([MCHb])) is currently lacking. We hypothesize that during the last half of incubation when the respiratory organ (the chorioallantoic membrane) envelops most of the egg contents, mean corpuscular indices will stabilize. Accordingly, Hct, [RBC] and [Hb] must also all change proportionally across development. Further, we hypothesize that the hematological respiratory variables develop and mature as a function of incubation duration, independently of embryonic growth. As predicted, a similar increase in Hct (from 18.7±0.6% on day 10 (d10) to 34.1±0.5% on d19 of incubation), [RBC] (1.13±0.03×10(6)/μL to 2.50±0.03×10(6)/μL) and [Hb] (6.1±0.2 g% to 11.2±0.1 g%) occurred during d10-19. Both [RBC] and [Hb] demonstrated high linear correlation with Hct, resulting in constant [MCHb] (~33 g% from d10 to d19). The decrease in MCV (from ~165 μ(3) on d10 to ~140 μ(3) on d13) and MCH (~55 pg to ~45 pg) during d10-13, may be attributed to a changeover from larger primary to smaller secondary and adult-type erythrocytes with MCV and MCH remaining constant (~140 μ(3) and ~45 pg respectively) for the rest of the incubation period (d13-19). Hematological respiratory values on a given incubation day were identical between embryos of different masses using either natural mass variation or experimental growth acceleration, indicating that the hematological variables develop as a function of incubation time, irrespective of embryo growth.     

Hematologic values of the endangered San Joaquin kit fox, Vulpes macrotis mutica

Between 1981 and 1982 blood samples were collected from 64 adult San Joaquin kit foxes, Vulpes macrotis mutica, in western Kern County, California. The goal of the study was to establish normal blood values for this endangered species, and to determine whether changes in them could be used to assess the possible effects of petroleum developments on these foxes. None of the values differed significantly between the sexes, or between foxes sampled in developed habitats compared with foxes sampled in undisturbed habitats. Mean values of Hb, MCH, MCHC, and WBC counts differed significantly between summer and winter. Average hematological characteristics were: RBC, 8.4 X 10(6)/microliter; Hb, 14.5 g/dl (summer), 15.6 g/dl (winter); PCV, 46.9%; MCV, 56.3 fl; MCH, 17.8 pg (summer), 18.4 pg (winter); MCHC, 31.2 g/dl (summer), 33.2 g/dl (winter); and WBC, 6,200/microliter (summer), 7,500/microliter (winter). Comparisons of hematological data for kit foxes, coyotes (Canis latrans), and wolves (Canis lupus) confirmed a previously published observation that within mammalian families RBC counts are correlated inversely with body weight, and that MCV is correlated directly with body weight.     

Hemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda

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 in classical hemochromatosis. Here, we studied the prevalence of both common and rare hemochromatosis gene variations in 51 PCT patients and 54 healthy controls of German origin. The frequency of the common HFE gene mutation C282Y was 15.7 % in PCT patients and 2.8 % in healthy control individuals (P < 0.001). By contrast, the frequencies of the common H63D mutation did not differ, and the allele frequencies of the less frequently observed sequence deviations as substitution S65C in the HFE gene and mutation Y250X in the TFR2 gene underlying hemochromatosis type 3 (HFE3) were < 0.02 both in PCT patients and controls. Our results comprise the first molecular studies of both common and rare hemochromatosis gene variants in German PCT patients, indicating a significant role of the C282Y mutation in the pathogenesis of PCT.     

Hemoglobin abnormalities

Summary In order to evaluate the polymorphism of hemoglobin in a population of Equatorial Africa, we undertook a prospective study of 146 births at a rural maternity hospital close to Brazzaville (P.R. Congo). This showed among the mothers 31 (22%) carriers of the sickle cell trait (AS), six with mutation, and two with -thalassemia triat. Among the children, 27 (18.5%) had sickle cell trait and one had sickle cell homozygosity. The frequency of the HbF Sardinia trait was 7.5%. This and other studies suggested a dilution gradient from Europe to Africa. Hemoglobin Bart's could be visually detected in 23.3% of the new-born babies. We attempted to distinguish between those infants with a high level of Hb Bart's (Bart's ++ group: 13.7%) and a group with a detectable Hb Bart's level that in our experimental conditions is between 1 and 2% (Bart's + group: 9.6%). Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were 88.6 ±5.7 fl and 29.0±2.1 pg in the Bart's ++ group; 94.5±10.9 fl and 30.6±4.1 pg in the Bart's + group; whereas they were 101.0±8.7 fl and 33.9±2.5 pg in the control group. Since iron dificiencies are very rare in new-borns and selecting according to published data on black people as homozygous -thalassemia of the type I (-/-), individuals of the Bart's ++ group whose MCV was below 95 fl and MCV below 30 pg, the gene frequency is estimated to be 34% and that of heterozygotes (-/) 45%. These high frequencies were confirmed in AS mothers: 45% showed a significant decrease of the S fraction.