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Fetal hemoglobin may be slightly or significantly elevated in post-natal life due to a number of causes. We report two novel mutations found on the promoter of the Aγ gene and summarize all common and rare determinants associated with hereditary persistence of fetal hemoglobin (HPFH) described thus far. Hematological and molecular analysis of the Aγ globin gene in two cases of HPFH. Comparison of the novel cases with all those described in the literature. We have found two novel mutations in three Italian patients with HbF values between 5.9% and 6.5% without an elevated HbA(2) and with normal hemoglobin parameters. In two probands (mother and son), a -197 C>T transition was observed, while in a single individual, a -113 A>G transition was present on the distal CCAAT box of the Aγ gene. As no other abnormalities were present in both γ-gene promoters and the changes are located on regulatory sequences, we may conclude that these mutations are responsible for the HPFH phenotype shown by the carriers. The laboratory should be able to discriminate between elevated HbF due to artifacts or to serious causes including bone marrow malignancies, aplastic anemia, and ß-thalassemia major or recessive traits such as ß-thalassemia minor, δß-thalassemia, or nonpathological conditions induced by mutations or polymorphisms of the γ-gene promoters that may even be beneficial when present in patients with thalassemia major or sickle cell disease and, in particular, when these patients are treated with hydroxyurea.

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OBJECTIVE: To review prevention data for hemoglobinopathies from Latium, a large Italian region with a considerable immigrant population and with a well-established regional prevention program. METHOD: All data pertaining to population screening for hemoglobinopathies in the Latium region were reviewed for the period 1994-2007. Screening was performed universally in secondary schools and to pregnant couples at the time of prenatal care. We have examined the trends in positive screening results as well as the type of hemoglobinopathies detected during the study period, and we have correlated them to the type of population (immigrant vs indigenous). RESULTS: From 1994 to 2007, 167 235 individuals were examined for carrier status for hemoglobinopathies, and 10 353 of them (6.2%) were immigrants. We have registered a threefold increase in rates of screen-positive subjects who belonged to ethnic minorities during the study period (from 2.7% in 1994 to 9.8% in 2007). Over half of the screen-positive subjects (5397/10 353) presented no hematological anomalies, 24% (n = 2472) had iron deficiency, and 24% (n = 2484) was classified as putative carriers. Among the last group, 22.6% were carriers of beta-thalassemia, 48% were suspected alpha-thalassemia carriers, and the remainder had less common hemoglobinopathies. While the prevention program resulted in nearly zero births of autochthonous newborns affected by severe hemoglobinopathies, a rise in number of affected individuals was noted among immigrants. Screening of secondary school students was accepted by 67% of immigrant parents, resulting in 9737 pupils screened between 2002 and 2006. CONCLUSION: Existing preventive programs for severe hemoglobinopathies should adapt to changes in population ethnicities. Screening for hemoglobinopathies at school age is an efficient strategy.

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BACKGROUND/AIMS: In chronic active liver diseases (CALD) with viral aetiology, a population of plasma cells localised in the piecemeal necrosis areas was previously detected by means of autoradiography after in vitro 3H-proline incorporation, a method which proved much more sensitive than conventional immunohistochemical procedures. These plasma cells, characteristically located in niches among hepatocytes, in close contact with collagen fibrils, have been hypothesised to exert a role in fibrogenesis stimulation, and particularly in collagen synthesis, possibly through secretion of lymphokines. Specifically, we investigated the presence of interleukin-1, well known to play a crucial role in inflammation and production of collagen by epithelial cells, and to be present in activated plasma cells of myeloma. METHODS: The immunohistochemical localisation of interleukin-1beta in biopsies of patients suffering from chronic active hepatitis was studied, using an affinity-purified rabbit polyclonal antibody. RESULTS: The strongest interleukin-1beta immunostaining was observed in the above-described plasma cell population, identified by anti-immunoglobulin antibodies, and 3H-proline incorporation. CONCLUSIONS: The ability of plasma cells to produce interleukin-1 during viral CALD suggests that in these pathologies plasma cells play a major role, mainly of paracrine nature. Interleukin-1, possibly together with other mediators, might in turn stimulate the production of collagen. Hepatocytes of the piecemeal necrosis area appear to be possible candidates for this synthesis, as they show a significant labelling after 3H-proline incorporation, which is absent from hepatocytes far from necrotic areas.

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BACKGROUND AND OBJECTIVE: beta thalassemia intermedia has its origins in compound heterozygosity for many different beta thal defects or in an interaction of a beta thal defect with altered alpha cluster. Two specific genetic associations (beta thal/beta(+) -101 C-->T and beta thal + alpha alpha alpha or alpha alpha alpha alpha) have been described in recent years as being determining a phenotype similar to that of simple beta thal heterozygote or, alternatively, a clinical picture of thalassemia intermedia. METHODS: A detailed study on this subject was carried out on 55 patients divided into 2 groups. Group I consisted of 20 patients, 17 of whom (Group Ia) had a beta thal/beta(+) -101 C-->T genotype and 3 (Group Ib) had a beta thal/beta IVS II-844 C-->G genotype. Group II consisted of 35 patients with beta thal association + alpha alpha alpha or alpha alpha alpha alpha. The methods of study have already been described in a previous issue. RESULTS: Thirty percent of group Ia and 25% of group II were virtually asymptomatic, while the others presented the thalassemia intermedia phenotype. This second phenotype is generally milder in patients of group I and even less so in those of group II. In the former there is a higher level of HbF; in the second there is more marked alpha/beta + gamma globin synthesis imbalance. The severity of the phenotype has no connection with that of the beta thal defect. The patients of group Ib all presented thalassemia intermedia. INTERPRETATION AND CONCLUSIONS: The definite clinical pictures of groups I and II are quite common in the Italian population and should therefore be well understood, especially for proper application of preventive measures against thalassemia major.

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