[Observations on human parvovirus B19 infection diagnosed in 2011]. / A 2011. évi B19 humán parvovírus-fertozésekrol szerzett tapasztalatok.

INTRODUCTION: The incidence of human parvovirus B19 infection is unknown. AIM: A retrospective analysis of clinical and laboratory findings was carried out in patients diagnosed with human parvovirus B19 infection in 2011 in a virologic laboratory of a single centre in Hungary. METHODS: Clinical and laboratory data of patients with proven human parvovirus B19 infection were analysed using in- and out-patient files. RESULTS: In 2011, 72 patients proved to have human parvovirus B19 infection with the use of enzyme immunoassay. The clinical diagnoses of these patients were as follows: human parvovirus B19 infection (30.6%), transient aplastic crisis (16.7%), arthritis (8.3%) and acute hepatitis (4.1%). Symptoms of each of the four phases of the infection occurred in various combinations with the exception of the monophase of cheek exanthema. This occurred without the presence of other symptoms in some cases. Leading symptoms and signs were exanthema (in 74.6% of cases), haematological disorders (in 69% of cases), fever (in 54.9% of cases) and arthritis (in 33.8% of cases). Several atypical dermatological symptoms were also observed. Acute arthritis without exanthema was noted in 8 patients. Of the 72 patients with proven human parvovirus B19 infection there were 7 pregnant women, and one of them had hydrops foetalis resulting spontaneous abortion. In 16 patients (22.5%) human parvovirus B19 IgG was undetectable despite an optimal time for testing. CONCLUSION: The observations of this study may contribute to a better recognition of clinical symptoms of human parvovirus B19 infection.

[The role of Helicobacter pylori infection in children with chronic immune thrombocytopenic purpura]. / A Helicobacter pylori szerepe a gyermekkori idiopathiás immunthrombocytopeniában.

UNLABELLED: Helicobacter pylori infection has been associated with immune thrombocytopenic purpura in adults, however, the few studies concerning this issue showed conflicting results in the paediatric field. Therefore, authors prospectively investigated the incidence of Helicobacter pylori infection and the effect of Helicobacter pylori eradication on platelet count recovery in children with immune thrombocytopenic purpura. PATIENTS AND METHODS: The study included 27 children with immune thrombocytopenic purpura (13 boys and 14 girls) with a median age of 8.2 years (range, 18 months-18 years). 38 healthy children (controls) were also enrolled (20 boys, 18 girls, median age, 9.6 years, range, 4-18 years). Helicobacter pylori infection was diagnosed using 13 C urea breath test. Eradication was assessed at 6 weeks following the end of the treatment by 13 C urea breath. RESULTS: 2 children out of 27 patients with immune thrombocytopenic purpura proved to be positive for Helicobacter pylori infection (7.7%) and were treated with combination therapy. Controls showed similar rate of Helicobacter pylori infection (3/38, 7.9%) in comparison to those with immune thrombocytopenic purpura. In the follow-up period (mean, 10 months, range, 6-14 months) platelets did not show any improvement in infected children following the eradication treatment and were identical to those of the uninfected patients. Eradication was successful in the 2 Helicobacter pylori infected patients with immune thrombocytopenic purpura. CONCLUSION: The results do not suggest a pathogenetic role of Helicobacter pylori infection in the etiology of immune thrombocytopenic purpura. Screening of Helicobacter pylori infection among paediatric patients with immune thrombocytopenic purpura is not recommended.

Carrier and prenatal diagnostic strategy and newly identified mutations in Hungarian haemophilia A and B families.

Deficiencies of blood coagulation factors VIII and IX (haemophilia A and haemophilia B) represent the most common inherited bleeding disorders with a wide range of causative mutations. Carrier and prenatal diagnostics are preferably performed by direct mutation detection; however, in certain situations, indirect family studies may also be useful. We aimed to utilize a combination of direct and indirect techniques for carrier and prenatal diagnostics in both haemophilias in a single national centre. Two hundred and eleven haemophilia A families were investigated by screening for inversions of introns 1 and 22, and by family studies using polymorphic markers. Twenty-eight haemophilia A and 39 haemophilia B families were investigated by Sanger-sequencing of the coding regions. Among severe haemophilia A families, frequencies of intron 22 and 1 inversions were 82 out of 145 (57%) and two out of 145 (1.4%). Sequencing of the entire coding region of the respective factor gene was performed and 12 (haemophilia A) and 5 (haemophilia B) previously unpublished disease-causing mutations were identified. For genetic markers used for haemophilia A indirect family testing, heterozygosity rates varied between 137 out of 327 [42% intragenic BclI restriction fragment length polymorphism (RFLP], 168 out of 254 (66% intragenic F8Civs13CA) and 202 out of 261 (77% extragenic DXS15CA) with a combined rate of 92% (intragenic markers) and 97% (all three markers). For male fetuses, prenatal diagnostics was provided to 43 haemophilia A families (n = 22 with direct mutation detection and n = 21 by indirect family testing) and to three haemophilia B families. The combination of direct and indirect molecular genetics approaches is a successful and cost-effective approach to provide carrier and prenatal diagnostics and risk assessment for inhibitor formation.

Analysis of large structural changes of the factor VIII gene, involving intron 1 and 22, in severe hemophilia A.

BACKGROUND AND OBJECTIVES: Hemophilia A (HA), the deficiency of coagulation factor VIII (FVIII), is the most common, sex-linked inherited bleeding disorder. The disease is caused by FVIII gene intron 22 inversion in approximately 50% of the patients, and by intron 1 inversion in 5% of the patients with severe HA. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22, and their extragenic copy located telomeric to the FVIII gene. The goal of the present study was to analyze the presence of large structural changes in the FVIII gene in patients with severe hemophilia A. DESIGN AND METHODS: We studied 104 unrelated, severe HA-patients or obligate carriers for the presence of intron 22 and intron 1 inversions by Southern blotting, long-distance polymerase chain reaction (PCR), and simple PCR. RESULTS: We found altered intron 22 restriction profiles by Southern analyses in 58 cases: 43 type 1, 11 type 2 inversions and 4 unusual patterns. Upon further examination of the last 4 cases, large deletions involving intron 22 were demonstrated in two cases. In the remaining two patients extra homologous regions were detected by Southern analysis, and long-distance PCR showed the presence of unaltered intra- and extragenic copies together with one inversion-affected copy, suggesting that an additional intronic fragment participated in the inversion process and was inserted in the genome. During screening for intron 1 inversion among 43 patients, who were intron 22 inversion negative, we identified only wild type individuals. INTERPRETATION AND CONCLUSIONS: The relatively large proportion of unusual patterns further supports the observation that the structure of FVIII intron 22 represents a hot spot for large gene rearrangements with various mechanisms, while intron 1 inversion seems to be not common in Hungary.

[Guillain-Barré syndrome in patients treated for Hodgkin disease]. / Guillain-Barré-szindróma kialakulása Hodgkin-kór miatt kezelt betegben.

INTRODUCTION: A 14-year-old boy treated with Hodgkin's disease developed muscular weakness and pain, hypotonia, abolished deep tendon reflexes. Examination of the cerebrospinal fluid showed albuminocytologic dissociation, the characteristic finding of Guillain-Barré syndrome. After high dose steroid treatment complete recovery occurred. DISCUSSION: Paraneoplastic neuropathies may develop in patients with cancer, Guillain-Barré syndrome occurs in patients with active Hodgkin's disease. CONCLUSIONS: Progressive neurological signs may indicate the presence of a malignancy, or in case of chemotherapy shows the activity of the tumour.

Severe coagulation factor V deficiency caused by 2 novel frameshift mutations: 2952delT in exon 13 and 5493insG in exon 16 of factor 5 gene.

A male infant with severe bleeding tendency had undetectable factor V activity. Sequence analysis of the proband's DNA revealed one base deletion in exon 13 (2952delT) and one base insertion in exon 16 (5493insG) in heterozygous form. Both mutations introduced a frameshift and a premature stop at codons 930 and 1776, respectively. The proband's father and mother were heterozygous for 2952delT and for 5493insG, respectively. Both mutations would result in the synthesis of truncated proteins lacking complete light chain or its C-terminal part. In the patient's plasma, no factor V light chain was detected by enzyme-linked immunosorbent assay. The N-terminal portion of factor V containing the heavy chain, and the connecting B domain was severely reduced but detectable (1.7%). A small amount of truncated factor V-specific protein with a molecular weight ratio of 236 kd could be immunoprecipitated from the plasma and detected by Western blotting. This protein, factor V(Debrecen), corresponds to the translated product of exon 16 mutant allele.