Cases Of Thalassemia Research Articles

Screening for thalassaemia among group of students of a higher institution – our experience

Introduction: Thalassaemia is an inherited blood disorder and is a significant public health alarm in Malaysia with many not knowing they are carriers of this haemoglobin disorders. Materials and methods: This study conducted a one off collection of blood samples from 72 Malays students of International Islamic University Malaysia (IIUM) in Kuantan. Blood samples were subjected to conventional haemoglobin analyses that include full blood count and picture, HPLC, Haemoglobin electrophoresis and H-inclusion test. All samples were also genotyped for alpha thalassaemia–1 of Southeast Asia (a-Thal1SEA). Result: There were 17(23.6%) students who were diagnosed as thalassaemia carriers. Out of this, four (5.5 %) and six (8.3 %) students were presumptive β-thalassaemia trait and Haemoglobin-E trait as determined by the HPLC assay respectively. Nine (12.5%) students were genotyped a-Thal1SEA among whom two were also β-thalassaemia carriers. All thalassaemia cases had MCH of < 27pg. Nonetheless, two out of six Haemoglobin-E trait and three out of nine a-Thal1SEA carrier had MCV value of >80fL. Two out of four (50%) presumptive β -thalassaemia trait and one out of six (17%) students of presumptive Haemoglobin-E trait had family history of thalassaemia respectively. Conclusion: The high occurrence of the three common types of thalassaemia carrier (β, Hb-E and a-Thal1SEA thalassaemia) in our small group of subjects could be due to better participation of students who had family history of thalassaemia. The study reaffirmed the importance of molecular study for detection of alpha-thalassaemia and the use of MCH value of <27pg rather than MCV value of < 80fL for prediction of thalassaemia.

Molecular Spectrum of α- and β-Globin Gene Mutations Detected in the Population of Guangxi Zhuang Autonomous Region, People's Republic of China

We studied 6,023 individuals diagnosed with anemia on the basis of hematological examinations. The study showed that the frequency of α-thalassemia (α-thal) carriers was 26.9% and β-thal carriers comprised 19.9% of the population of Guangxi Zhuang Autonomous Region, People's Republic of China (PCR). The diagnosed α-thal anomalies were related to six gene mutations and 16 genotypes, whereas the β-thal were related to 10 gene mutations and 65 genotypes. The four most common mutations [codons 41/42 (–TTCT), codon 17 (A>T), −28 (A>G) and IVS-II–654 (C>T)] accounted for 86.38% of the β-globin gene mutations. Risk analysis of mutation alleles in thalassemia cases identified four mutations (–α3.7, −α4.2, ααWestmead and ααCS) that were associated with α-thal intermedia, with an odds ratio (OR) of 62.41-32.68. Four high-risk mutations, namely, codon 26 (G>A), −28, codons 41/42 and codon 17, were associated with β-thal major (β-TM), with an OR of 3.93-2.20. The present study provides important genetic information on thalassemia in this population.

Look for the silent when other tests cannot speak (a case of unexpected rare thalassaemia)

Microcytic anaemia is a common consultation in haematology practice. The common causes are iron deficiency, thalassaemia or anaemia of chronic disease. The diagnosis can be directly obtained through appropriate laboratory tests. However, in the absence of a positive history or a laboratory test, the diagnosis may be obscure and more sophisticated laboratory tests may be required. A 27-year-old Australian woman from a Scottish-Welsh ancestry was referred with long standing microcytic anaemia. The laboratory tests including iron studies, haemoglobin HPLC and electro-phoresis were normal and repeated twice to exclude pre-analytical and analytical variability. Other causes of microcytic anaemia including lead toxicity, copper or zinc deficiency, chronic inflammatory disease or sideroblastic anaemia were excluded. The patient’s blood sample was sent to the Royal Prince Alfred hospital for molecular testing for possible underlying thalassaemia. A heterozygous large deletion in the beta globin region with an intact alpha globin using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) was detected. The finding supports the diagnosis of epsilon-gamma-delta-beta (eγδβ)o thalassaemia. This type of normal HbA2 beta thalassaemia or silent beta thalassaemia has been previously reported in a family with Scottish-Irish ethnic background in NSW. 1

Hemoglobin F level in different hemoglobin variants

BackgroundFetal hemoglobin (HbF) levels in different hemoglobin variants in Osogbo, Nigeria, were estimated using two principal methods of estimation using existing information for HbF concentration and distribution of various hemoglobin variants in the area, as well as diagnosed cases of thalassemia. Two hundred and sixty samples collected from HbSS, HbSC, HbAA, HbAS, and HbAC subjects were analyzed. HbF level and hemoglobin type were determined in this study.MethodsThe hemoglobin type was determined using cellulose acetate electrophoresis at an alka-line pH, and HbF was determined by the acid elution and alkaline denaturation methods.ResultsThe mean±SD of HbF in the respective hemoglobin variants was as follows: HbSS, 2.09±1.94%; HbSC, 0.85±0.54%; HbAA, 0.69±0.46%; HbAS, 0.52±0.31%; and HbAC, 0.57±0.26%. The mean HbF level across the hemoglobin variants was statistically significant (P<0.05). Investigating the sex distribution of the HbF level in the studied population revealed a slightly higher mean HbF level in females than in their male counterparts.ConclusionWithin the study population, the HbF level was found to be highest in HbSS and lowest in HbAS. The two methods of estimating HbF are equally reliable, since there was no significant difference between the results obtained from the two methods.

Transfusion-induced hemoglobinopathy in patients of beta-thalassemia major

Apparent hemoglobinopathy acquired after blood transfusion is an uncommon cause of diagnostic dilemma resulting in repeated testing and delay in the diagnosis. Out of the 1530 hemoglobin (Hb)-high-performance liquid chromatography (HPLC) performed at our hospital (May 2009 to April 2010), 3 pediatric cases of thalassemia major were detected having posttransfusion hemoglobinopathy with HbS ranging from 9.9% to 18.5%. In all three cases, there was no variant hemoglobin in earlier documented Hb-HPLC. It is important to be aware of and consider apparent transfusion-induced hemoglobinopathy in patients with unusual percentage of variant hemoglobin to avoid unnecessary treatment and counseling.

Quantitative analysis of Hb Bart’s in cord blood by capillary electrophoresis system

It has long been recognized that the presence of hemoglobin (Hb) Bart's in newborn's blood is associated with α-thalassemia. However, the automated high-performance liquid chromatography or low-performance liquid chromatography system is unable to quantify the amount of Hbs Bart's and H, which are eluted at the retention time close to 0min. This study used automatic capillary electrophoresis (CE) system to diagnose various types of α-thalassemia in 587 cord blood samples, including 429 normal α-globin genotype, 120 cases of thalassemia with one α-globin gene defect, 34 cases with two α-globin genes defect, and four cases with three α-globin genes defect. The result showed that the level of Hb Bart's in cord blood was increased accordingly with the increasing numbers of the defective α-globin genes. In addition, Hb Bart's level at 0.2%, as measured by CE, can be used as a cut-off point for α-thalassemia diagnosis in newborns.

Thalassaemia: Its diagnosis and interpretation in past skeletal populations

ABSTRACTThe diagnosis of thalassaemia in archaeological populations has long been hindered by a lack of pathogonomic features, and the non‐specific nature of cribra orbitalia and porotic hyperostosis. In fact, clinical research has highlighted more specific diagnostic criteria for thalassaemia major and intermedia based on changes to the thorax (‘rib‐within‐a‐rib’ and costal osteomas). A recent re‐examination of 364 child skeletons from Romano‐British Poundbury Camp, Dorset revealed children with general ‘wasting’ of the bones and three children who demonstrated a variety of severe lesions (e.g. zygomatic bone and rib hypertrophy, porotic hyperostosis, rib lesions, osteopenia and pitted diaphyseal shafts) that are inconsistent with dietary deficiency alone, and more consistent with a diagnosis of genetic anaemia. Two of these children displayed rib lesions typical of those seen in modern cases of thalassaemia. The children of Poundbury Camp represent the first cases of genetic anaemia identified in a British archaeological population. As thalassaemia is a condition strongly linked to Mediterranean communities, the presence of this condition in a child from England, found within a mausoleum, suggests that they were born to wealthy immigrant parents living in this small Roman settlement in Dorset. This paper explores the diagnostic criteria for genetic anaemia in the archaeological literature and what its presence in ancient populations can contribute to our knowledge of past human migration. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Molecular characterization of sickle cell anemia in the Northern Brazilian state of Pará

To assess alpha+-thalassemia deletion alleles, beta-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belém, Pará State, for their possible effects on the patients' survival. -alpha(3.7), -alpha(42), -alpha(20.5), and -(MED) alpha+-thalassemia deletion alleles were investigated using multiplex gap-PCR method. Characterization of beta-thalassemia mutations was made by direct genomic sequencing of the beta-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5'gammaG, (2) HindIII-gammaG, (3) HindIII-gammaA, (4) HincII-psibeta, (5) HincII-3'psibeta, and (6) HinfI-5'beta] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -alpha3.7 thalassemia. Sixteen of those (76%) were heterozygous (-alpha3.7/alphaalpha) and 5 (24%) were homozygous (-alpha3.7/-alpha3.7). -Alpha(4.2), -alpha(20.5) and -(MED) deletions were not found. Nine cases of sickle cell-beta thalassemia were found and four different beta-thal mutations were identified: beta(+) -88 (C>T), 3.8%; beta(+) codon 24 (T > A), 1.5%; beta(+) IVSI-110 (G > A), 0.7% and beta (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -alpha(3.7) deletion, beta-thalassemia and HHB*S haplotypes distribution. Our results suggest that although alpha- and beta-thalassemia and betaS haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival.

Diagnostic value of fingerprint patterns: An explorative study on beta-thalassemia diagnosis

Rapid diagnosis of major beta thalassemia along with certain preventive measures is of utmost significance. The present study aims to compare the fingerprints in Major beta thalassemic patients (67) and in their parents (76 with minor thalassemia) with the normal fingerprints of control group (144). A forensic medical examiner determined fingerprint types of arch, loop, whorl and other types. Like normal individuals, loop fingerprint pattern was found to be the most common fingerprint type among thalassemic patients. However, the number of whorl fingerprints in all fingers in thalassemic patients was greater than that of normal individuals and the number of loop fingerprints was smaller (p < 0.05). Arch type fingerprint pattern was less frequent in major thalassemic patients compared to minor thalassemic ones (p < 0.05). The findings show that the number of whorl fingerprint patterns in thalassemic patients was greater than that of normal individuals, while the number of loop fingerprint patterns being smaller and the frequency of arch fingerprint pattern in patients with major thalassemia was lower than that of minor thalassemic patients. Therefore, one may choose fingerprint pattern as a simple, affordable and appropriate screening method to help detect the afflicted patients and prevent severe cases of thalassemia.

A Rapid Single-Tube Multiplex Polymerase Chain Reaction Assay for the Seven Most Prevalent α-Thalassemia Deletions and αααanti 3.7 α-Globin Gene Triplication

α-Globin gene triplications may exacerbate the α chain and β chain imbalance in β-thalassemia (β-thal) and may compensate for the effect of α-globin gene deletion in α-thal. Identification of an α-globin gene triplication is, therefore, valuable in predicting the clinical phenotype of the thalassemias. To be able to detect α-globin gene triplications, we have modified an existing multiplex polymerase chain reaction (PCR) assay for the seven most prevalent α-globin gene deletions by incorporating two triplication-specific primers and concurrently substituting one of the original primers by a newly designed primer. This modified multiplex PCR assay was evaluated by performing the assay on archival DNA samples and on peripheral blood samples from 163 suspected thalassemia cases. It was found to function properly. Our assay thereby represents the first multiplex PCR assay that can detect both the seven most prevalent α-globin gene deletions and the αααanti 3.7 α-globin gene triplication in a single-tube reaction.

English

&nbsp; Ninety-eight postnatal and six prenatal cases&nbsp;of thalassemia&nbsp;were studied&nbsp;by the reverse dot-blot hybridization technique&nbsp;in the city of Gaziantep, Turkey. We found the following mutations:&nbsp;IVS 1.110 (G&gt;A) in 29.1%, IVS 2.1 (G&gt;A) in 12.3%, IVS 1.1 (G&gt;A) in 7.7%, Codon 8 (&minus;AA) in 5.6%,&nbsp;-30 (T&gt;A) in 4.6%, IVS 1.6 (T&gt;C) in 4.6%,Codon 39 (C&gt;T) in 3.6%, Codon 44 (-C) in 3.1%, IVS 2.745 (C&gt;G) in 1.5%, Codon 8/9 (+G) in 2.1%, Codon 36/37 (-T) in 2.1%, IVS 1.5 (G&gt;C) in 2.1%, Codon 22 (7pb del)&nbsp;in 0.5%,&nbsp;Codon 5 (-CT)&nbsp;in 0.5% while 20.9% were undetermined. 54 of the thalassemia patients were homozygotes, 12 were compound heterozygous and 31 were heterozygotes. In one allele of 5 thalassemia patients, &alpha;-thalassemia mutation (3.7 single gene deletions in 1 patient, anti-3.7 gene triplication in 4 patients) was determined at the same time. Finally, this is the first comprehensive study in this region and percentage of &alpha; and &beta;- globin genes mutation is 2.6 and 79.4%, respectively. &nbsp; Key words:&nbsp;&alpha;- thalassemia,&nbsp;&beta; -thalassemia, DNA, mutation, polymerase chain reaction.

Clinical, hematologic and molecular variability of sickle cell-β thalassemia in western India

BACKGROUND:Sickle cell-β thalassemia (HbS-β thalassemia) is a sickling disorder of varying severity, which results from compound heterozygosity for sickle cell trait and β thalassemia trait. The present study was undertaken to determine the genetic factors responsible for the clinical variability of HbS-β thalassemia patients from western India.MATERIALS AND METHODS:Twenty-one HbS-β thalassemia cases with variable clinical manifestations were investigated. The α and β globin gene clusters were studied by molecular analysis.RESULTS:Thirteen patients showed milder clinical presentation as against eight patients who had severe clinical manifestations. Four β thalassemia mutations were identified: IVS 1-5 (G→C), codon 15 (G→A), codon 30 (G→C) and codon 8/9 (+G). α thalassemia and XmnI polymorphism in homozygous condition (+/+) were found to be common among the milder cases. The βS chromosomes were linked to the typical Arab-Indian haplotype (#31). Framework (FW) linkage studies showed that four β thalassemia mutations were associated with different β globin gene frameworks. Linkage of codon 15 (G→A) mutation to FW2 is being observed for the first time.CONCLUSION:The phenotypic expression of HbS-β thalassemia is not uniformly mild and α thalassemia and XmnI polymorphism in homozygous condition (+/+) are additional genetic factors modulating the severity of the disease in the Indian subcontinent.

Frequency of Positive XmnIGγ polymorphism and coinheritance of common alpha thalassemia mutations do not show statistically significant difference between thalassemia major and intermedia cases with homozygous IVSII-1 mutation

From 362 thalassemia cases referred to adult thalassemia clinic of the Iranian blood transfusion organization (IBTO) for genotyping, 103 cases (28.5%) had a common primary disease factor, IVSII-1 mutation in homozygous state. 61 (59.2%) of these individuals represented thalassemia major and 42 (40.8%) thalassemia intermedia clinical phenotype. To re-evaluate our current diagnostic criteria, XmnI Gγ polymorphism and coexistence of alpha thalassemia mutations, frequently recalled as important factors modifying the clinical phenotype of homozygous beta zero thalassemia cases in our country, were examined in both groups. No statistically significant difference in the frequency of positive XmnI Gγ polymorphism was observed between thalassemia intermedia and thalassemia major patients. Double gene deletion -- Med was observed in only one thalassemia major case, while − a 3.7 in heterozygous state (− a 3.7/aa) was identified in 6 (9.8%) of thalassemia major and 8 (19%) of thalassemia intermedia patients. − a 4.2 was observed in only one thalassemia major case. No statistically significant difference in the frequency of coinheritance of alpha thalassemia was observed between the two groups. These results imply that other interacting mechanisms which modify the phenotype of thalassemia patients is still in the dark in our current diagnostic criteria of thalassemia.

Survey on thalassemia among people of reproductive age in Guilin City, Guangxi, China

To study the present situation of thalassemia among people at reproductive age in Guilin city. A complete red blood cell mean cell volume (RBCMCV) was detected as well as hemoglobin electrophoresis analysis were done for all samples. Suspected alpha or beta thalassemia cases, were screened out and alpha and beta thalassemia genes were detected by PCR-RDB. Among 1580 cases, 79 cases were detected a thalassemia gene positive, with the detection rate as 5.00%. The detection rates on a thalassemia were 5.32%, 4.68% in males and females, but no significant difference (chi2 = 3.04, chi2 < chi0.05 (1) = 3.84, P > 0.05). 114 cases were detected carrying beta thalassemia gene with the detection rate as 7.22%. The detection rates on beta thalassemia were 7.85%, 6.58% in males and females, with no significant difference (chi2 = 0.95, chi2 < chi0.05(l) = 3.84, P > 0.05). The overall detection rate of thalassemia was 12.22% (193/1580). Alpha thalassemia were found to have had ten genotypes, with --SEA/alphaalpha the most common one and the detection rate was 3.54%. -Alpha(3.7)/alphaalpha appeared the majority in the static alpha thalassemia and --SEA/alphaalpha took the majority in the light a thalassemia, while --SEA-alphaCS was the major one in the intermedia alpha thalassemia, with gene contributions of 7.59%, 70.88% and 2.53%. Beta thalassemia was detected having seven genotypes,with CD41-42 (-TTCT) the most common one in beta thalassemia, and the detection rate was 3.16%. The commonly seen three mutations, CD41-42 (-TTCT), CD17 (A-->T) and IVS-II-654 (C-->T) were accounted for 87.71% of beta thalassemia. The detection rate on thalassemia a and beta combination was 0.63%. The detection rate of thalassemia among people at productive age in Guilin city was relatively high.

Thalassaemia management in Hong Kong

Thalassaemia is the most common genetic disease in the world and is especially prevalent in the Asian region. The management of thalassaemia is the combination of public health and clinical efforts. Advances in prenatal diagnosis have made it theoretically possible to reduce new cases of severe thalassaemia to negligible levels. However, this can only be achieved with good maternity public health network and good public education. Thalassaemia major patients rely on chronic transfusion for survival. A safe and affordable blood supply is the prerequisite for any modern thalassaemia management. The most common cause of death in thalassaemia in developed countries is heart failure relating to haemosiderosis. The availability of new oral chelators that can effectively remove cardiac iron and the advent of magnetic resonance imaging monitoring to assess cardiac iron will hopefully give significant impact on thalassaemia survival.

The novo 4 BP deletion in the codons 20/21 (−TGGA) at the first exon of the β-globin gene causing a β0-thalassemia in a Spanish male

Dear Editor, This paper reports a novel mutation in the coding region of the " gene. This mutation is a frameshift deletion of 4 bp (−TGGA) in the codons 20/21 of the first exon of this gene and this produces a "-thalassemia phenotype. "-Thalassemias are a heterogeneous group of autosomal recessive disorders characterized by deficient (") or absent (") "-globin chain synthesis. The large majority of the β-thalassemia defects are single nucleotide mutations that affect one of the different molecular processes involved in "-globin gene expression (transcription, pre-mRNA processing, and translation). Only a minority of "-thalassemia is produced by deletions of the structural gene. More than 200 different " gene mutations have been described so far. The largest number of "thalassemia results derived from so-called nonsense and frameshift mutations, which interrupt the normal translation of mRNA [1, http://globin.cse.psu.edu/globin/hbvar]. An asymptomatic 29-year-old man, born in Galicia (northwest of Spain), was studied following a routine blood smear analysis, which revealed microcytic and hypochromic red cells. He was referred to us as a suspected case of thalassemia. Diagnosis of β-thalassemia was performed measuring red cell indices on an automated blood cell counter (COULTER GEN-S, Coulter, Hialeah, FI, USA). The propositus exhibited a discreet anemia (Hb 12.5 g/dl and packed cell volume 38.2%); an elevated red cell count (6.39×10/l); a lower mean cell volume (59.7 fl) and reduced mean cell hemoglobin (19.6 pg). The HbA2 and HbF levels were obtained by high performance liquid chromatography (HPLC-VARIANTTM BioRad Laboratories, Hercules, CA, USA) and while HbA2 concentration was increased (5.1%) HbF level was normal (1.3%). His reticulocyte count was 0.96% (this relatively low count may be a possible consequence of bone marrow dyserythropoiesis). The subject did not show ferropenic anemia (ferritin 525 ng/ml) and the total bilirubin concentration was 1.07 mg/dl. The blood smear showed microcitosis, hypochromia, and basophilic stippling. The propositus did not show splenomegaly, hematological data, and clinical evolution was steady since 2002 (carrier of a "-thalassemia). For molecular study, DNAwas extracted from peripheral blood leukocytes using the salting out extraction procedure [2]. Initial screening, performed by real time polymerase chain reaction (RT-PCR Light Cycler, Roche) [3] and polymerase chain reaction-amplification reaction mutations system (PCR-ARMS), testing the most frequent "-thalassemia mutations in the Mediterranean area were negative [4, 5]. Finally, the characterization of the mutation was carried out by sequencing. The "-globin gene was amplified using the following primers: "1F, 5′-TCC TAA GCC AGT TGC CAG AAG-3′ [specific for the 5′ region of the "-globin gene (from nt −160 to −142)] and "1R, 5′-TCATTC GTC TGT TTC CCA TTC TAA AC-3′ (from nt +610 to +585) (all nt positions are given relative to the CAP site=nt1). The PCR product (770 bp long) was treated with the ABI PRISMTM dRhodamine Terminator Cycle Sequencing Ann Hematol (2008) 87:63–65 DOI 10.1007/s00277-007-0340-4

Genotypic Correlation Between Six Common β-Thalassemia Mutations and the XmnI Polymorphism in the Moroccan Population

β-Thalassemia (thal) is the most common recessive inherited disorder in Mediterranean populations. It is estimated that the frequency of this disease in the Moroccan population is between 1.5 and 3.0%. Severe forms of homozygous thalassemia cases require expensive and technically demanding curative (bone marrow transplantation) or palliative (chronic transfusion/chelation) therapies. The −158 (C→T) polymorphism of the Gγ-globin gene (XmnI polymorphism) is known to ameliorate the severity of the disease because of it strong association with an increased production of fetal hemoglobin (Hb F). Among the many known mutations in Morocco, six are common [codon 39 (C→T), frameshift codon (FSC) 8 (−AA), IVS-II-745 (C→G), FSC 6 (−A), −29 (A→G) and IVS-I-1 (G→A)]. In this study, we have investigated, in 82 Moroccan β-thalassemic chromosomes, the correlation between the six common mutations and the XmnI polymorphism using the Fisher exact test. The XmnI polymorphism was divided into two categories, (XmnI [+] and XmnI [−]) and the six common Moroccan mutations into two groups (group I with FSC 8 and group II without FSC 8). Correlation was carried out between the XmnI [+] category and the six common mutations individually that showed that 68% of chromosomes in the XmnI [+] category had the FSC 8 (−AA) mutation. The results reported here show that there is a positive correlation between the XmnI polymorphism and FSC 8 mutation in linkage with haplotype IV [− + − + + − +] (p <10−5). In conclusion, molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological Hb F switching by hydroxyurea (HU). In the Moroccan population, a good response to HU treatment should be suspected in cases with the −158 (C→T) polymorphism in linkage with haplotype IV and internal β-globin gene framework 3.

Augmentation de l’hémoglobine A 2 au cours du pseudoxanthome élastique

Pseudoxanthoma elasticum (PXE) is normally associated with mutations in the ABCC6 gene. A PXE phenotype without mutations in ABCC6 has been described in Greek and Italian patients presenting with beta thalassemia. We attempted to determine the incidence of beta thalassemia in a cohort of French patients with PXE.Fifty patients with PXE were included in the study. Laboratory examinations comprised hemoglobin electrophoresis, ABCC6 gene study and in some studies: mutation analysis, beta-globin gene.No cases of beta thalassemia were diagnosed in this cohort of French patients with PXE. However, 20% of the latter exhibited a significant but isolated (i.e. without microcytic anemia) increase of hemoglobin A2 (HbA2). Statistical comparisons showed no difference in terms of geographical origin or severity of PXE between patients with high levels of HbA2 and those with normal levels of HbA2 other than the extent of cutaneous involvement. Study of the beta-globin gene displayed mutations only in the two patients with the highest recorded levels of HbA2. ABCC6 + beta-globin digenism was ruled out of the pathogenesis of PXE.The PXE phenotype seen in some patients with beta thalassemia appears to be associated with epigenetic modification of ABCC6 transcription and depends specifically on the beta globin locus. Isolated increase in HbA2 is probably a laboratory marker for PXE. Here again, a functional epigenetic reaction between ABCC6 and the beta-globin locus was suspected. However, these reciprocal interactions are clearly unequal since the change in ABCC6 transcription occurring during the course of beta thalassaemia is responsible for a PXE phenotype while increased HbA2 during the course of PXE has no clinical consequences.

Management of splenic abscess in children by percutaneous drainage

Background/Purpose Isolated splenic abscesses are rare in pediatric patients. The recommended treatment in the literature has been in favor of splenectomy, although conservative treatment with splenic preservation is being increasingly reported. We report successful management of 4 pediatric patients with splenic abscess by needle aspirations and antibiotics. Materials and Methods Four children (aged 7-11 years; male-female, 3:1) were admitted in our institution with history of high-grade fever with chills, anorexia, left hypochondrial pain, and splenomegaly. One child was a known case of thalassemia, and one had a history of typhoid fever. The others did not have any predisposing condition. Ultrasonography (USG) and computed tomographic scan of the abdomen showed a solitary abscess in the spleen in 2 patients and multiple abscesses in the other 2. Ultrasonography-guided needle aspiration in 3 cases revealed purulent fluid, which, on culture, grew Escherichia coli in 1 case, Salmonella paratyphi A in 1 case, but sterile in 1 case. Blood culture was sterile in all the cases, but Widal's test was positive in 2 patients. Treatment protocol included USG-guided needle aspiration of pus along with intravenous ceftriaxone, metronidazole, and amikacin for 3 to 12 weeks. Results All 4 patients showed a good response to conservative treatment. Serial USG showed gradual resolution of abscess, and none was subjected to splenectomy. Conclusion Isolated splenic abscess in children can be successfully treated with needle aspirations and intravenous antibiotics, thereby avoiding splenectomy.

Preimplantation Genetic Diagnosis (PGD) for B Thalassemia with or without HLA typing

Preimplantation Genetic Diagnosis (PGD) for β Thalassemia reveals a valid option for the prevention of the birth of an affected child. Preimplantation Genetic Diagnosis is also developed as a therapeutic tool for the cure of an affected child when combined with HLA typing. The purpose of the present report is to document our experience on PGD and PGD+HLA typing for β Thalassemia cases applied to our center.