No abstract

The changes in bone mineral density (BMD) measured by single photon absorptiometry (SPA) using two observations conducted over a period of 2 years were examined in 54 thalassemic subjects [30 F(A) and 24 M(B)] with a chronological age ranging from 2.6 to 22.6 years and in 27 sex- and age-matched controls (C). Each category (A, B and C) was divided into three groups according to pubertal signs: pre-pubertal subjects (A1, B1 and C1); peri-pubertal subjects (A2, B2 and C2) and pubertal subjects from the first observation (A3, B3 and C3). Furthermore, each group of patients was divided into sub-groups on the basis of haematological phenotypes, those with a more severe form were called beta0/beta0 while those with other forms were called "others". The most significant findings were the following: the presence of a more severe reduction of the bone mineral density in patients with the beta0/beta0 phenotype than in patients with the "others" phenotype; patients with hypogonadism corresponded to the beta0/beta0 phenotype, while those with spontaneous puberty corresponded to the "others" phenotype. In conclusion, since puberty and the degree of bone mineral density are related to the haematological phenotype, puberty (spontaneous or induced) positively influences the bone mineral density only at the start of puberty, while subsequently, the degree of osteoporosis is the expression of widespread and chronic systemic damage due to the haematological phenotype.

We characterized mutations and haplotypes of the delta-globin gene (HBD, MIM# 142000) in two regions of southern Italy. Mutations were discovered by screening for individuals with Hb A2<2%. In Basilicata, about 10,000 students were screened and 53 carriers in 43 unrelated families were diagnosed; in Campania, cases were referred through a routine thalassemia counseling service. Twelve alleles were detected. Four were novel variants [Hb A2-Metaponto (g.238C>A), Hb A2-Campania (g.302C>A), Hb A2-Lucania (g.393C>G), and Hb A2-Capri (g.443G>T)]. Hb A2-Lucania was not inherited but had arisen in the propositus. Two were novel mutations in the noncoding regions: the substitutions IVS2+6T>A, presumably affecting the splicing, and g.-126A>T in the GATA motif presumably affecting transcription. All novel alleles were found associated with haplotypes common in the Mediterranean area. The remaining six were alleles already described. The Hb A2-Yialousa (g.82G>T) was the most prevalent (42/63 families). Recurrent homologous crossing-over events have, most likely, linked this allele to Haplotypes IX (24 families), IV (10 families), or III (seven families). The ratio of Haplotypes IX:IV:III was about the same in the two regions. The rare allele Hb A2-NYU (g.39T>A) was found in 11 families from Basilicata associated with Haplotype I. All the 11 families lived in a restricted area extending from the Ionian Coast for 15 km along the Angri and Sinni Rivers. A founder effect most probably gave origin to this isolated group. The remaining four alleles were rare: the 7.2-kb deletion Corfù type (HBD g.-5946_1262del), Hb A2-Mitsero (g.14C>T), Hb A2-Etolia (g.385T>C), Hb A2-Coburg (g.1376G>A). Correlation between genotype and phenotype was established in 103 carriers.

We detected Hb D-Los Angeles [beta 121(GH4)Glu-->Gln], the most common hemoglobin variant after Hb S and Hb Lepore-Boston, in six unrelated families in Southern Italy. Ten patients were studied; eight patients were heterozygotes and two were compound heterozygotes for the hemoglobin variant and the beta-thalassemia codon 39 (C-->T) nonsense mutation. The beta-globin gene sequence was characterized by polymerase chain reaction direct sequencing; restriction fragment length polymorphisms were defined by Southern blot analysis. The gene variant, due to the GAA-->CAA substitution at codon 121, was found in association with the 5' subhaplotype [+ - - - -] and the beta-globin gene framework 1; in addition, it was found to be associated with the absence of Ava II/phi beta and Xmn I/5'G gamma, and with the presence of Hpa I/3' beta. This restriction fragment length polymorphism haplotype is common in the Mediterranean area as well as in other populations. The findings are equally compatible with an independent origin in the Mediterranean area or with origin in Asia and subsequent spread to Italy.

This study showed that the administration of DFO for 5 d a wk in combination with daily administration of DFP at 75 mg/Kg seemed to be the most efficacy and rapid method for reducing iron overload at liver and heart level. Furthermore, the use of different schedules of combined DFO and DFP administration was not associated with different incidence of adverse effects between the groups.