Pérsio Roxo

Chronic granulomatous disease in Latin American patients : Clinical spectrum and molecular genetics

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by early onset of recurrent and severe infections. The molecular defects causing CGD are heterogeneous and lead to absence, low expression, or malfunctioning of one of the phagocyte NADPH oxidase components. The aim of this study was to analyze the clinical features and to investigate the molecular genetic defects of Latin American patients with CGD.

Lung function in hyper IgE syndrome.

Pneumatoceles and bronchiectasis are secondary complications of respiratory infections in patients with hyper IgE syndrome (HIgES).

Allergic and Immunologic Parameters in Patients with Fanconi`s Anemia

Background: Fanconi`s anemia (FA) is a rare recessive chromosomal instability disorder, characterized by progressive bone marrow failure and congenital defects. Patients with FA present with recurrent infections, particularly those of the respiratory tract. Objective: The aim of the present study was to evaluate whether patients with FA have altered antibody-mediated immune responses. Methods: A group of 12 patients with FA, 5–32 years old (6 males) was studied. Serum levels of IgG, IgM, IgA and IgG subclasses, isohemagglutinin titers and specific IgG antibodies to poliovirus and measles were determined using standard methods. Immediate skin tests to common inhalant allergens were performed, and total and specific serum IgE was quantitated using a fluoroenzymatic assay (Uni-CAP, Pharmacia). Antipneumococcal antibodies were measured by ELISA before and 4–8 weeks after immunization with pneumococcal vaccine (Pneumo 23, Pasteur Mérieux Connaught). Responses to serotypes 1, 3, 5, 6B, 9V and 14, which are the most prevalent in our country, were studied. Results: Ten patients had elevated IgE levels in sera, and 7 of them had detectable specific IgE and positive immediate skin tests. An inadequate response to pneumococcal vaccination was found in 2 of the 12 patients. Isohemagglutinin titers and levels of IgG, IgM, IgA and IgG subclasses and antipoliovirus and antimeasles antibodies were within the normal limits for age in all patients. Two patients had undetectable IgG4 levels (below 5 mg/dl). Conclusions: The results indicate that a proportion of patients with FA (2/12) in our study had inadequate responses to pneumococcal vaccination. No other significant abnormalities of the immune system were found in these patients.

Renal Abscess in Hyper-IgE Syndrome

Kidney disease due to Aspergillus fumigatus is a rare finding in hyper-IgE syndrome. We report a patient with autosomal dominant hyper-IgE syndrome, recurrent pneumonia, and acute necrosuppurative pyelonephritis caused by Aspergillus fumigatus with a fatal outcome. We emphasize the severity and the difficulties in the management of renal complications that could be limiting the survival of these patients.

Unusual presentation of brain aspergillosis in chronic granulomatous disease.

Aspergillus is a frequently observed pathogen in patients with chronic granulomatous disease. We report on a patient with chronic granulomatous disease and severe brain aspergillosis with an unusual presentation and favorable course. We discuss the impact of this infection on morbidity and mortality, adequate therapeutic management, and the need to investigate a possible fungal infection, despite nonspecific signs.

Genomic instability in Hoyeraal–Hreidarsson syndrome

To the Editor: Much attention has been paid to rare diseases that evolve with impaired competence for telomere maintenance, as these conditions may unravel keystone genetic events related to cell aging and senescence. This topic was recently discussed in Pediatric Blood & Cancer by Pavesi et al. [1], who assessed telomere length in bone marrow (BM) failure syndromes including dyskeratosis congenita (DKC), a genodermatosis characterized by progressive BM failure and pancytopenia. Both DKC and Hoyeraal–Hreidarsson syndrome (HHS) are uncommon diseases associated with aging and premature short telomeres. HHS is an exceedingly rare condition that displays all manifestations of DKC with additional neurological deficits and immunodeficiency [2]. The X-linked forms of both diseases usually show distinctive mutations in the DKC1 gene, located on Xq28. This gene encodes a highly conserved nucleolar protein, called dyskerin, which is essential for ribosome biogenesis and telomerase maintenance [3,4]. In addition to impaired telomere maintenance, accumulation of chromosomes with aberrant fusions and rearrangements in BM has been previously reported in DKC patients [5] but not in HHS affected children. Indeed, besides the shared DKC1 mutation, little is known about how far both conditions are similar at the genetic and epigenetic levels. Therefore, we describe some particular cytogenetic findings on BM that may point to genomic instability in HHS. A 7-year-old male was referred with previous history of several recurrent and severe infections since his first month of life. His neurological development was clearly delayed by the age of 2.5 years. A brain MRI revealed a significant cerebellar hypoplasia. At admission, weight and stature were below percentile 3, nails had evident dystrophy and leukoplakia was present on the tongue (Fig. 1). Initial blood count revealed pancytopenia; both BM aspirates and biopsy showed a hypoplastic BM, with normal cell development. Immunological tests revealed abnormal cellular and humoral immunity, with low levels of IgG2. Preand post-immunization levels of IgG to pneumococcal polysaccharides measured by ELISA were significantly low for all 23 tested serotypes. Lymphocytes subpopulations measured by flow cytometry were very low, especially CD4þ, CD8þ, and CD19þ cells, with a reduced CD4þ/CD8þ rate. Mutation analysis of the DKC1 gene was targeted to the c.1058C>T. Restriction enzyme digestion of the relevant PCR product indicated this hemizygous mutation in the DKC1 gene, responsible for the p.Ala353Val amino acid substitution. This finding was confirmed by direct DNA sequencing. The mother of the index case was heterozygous for the mutation. Fluorescence in situ hybridization (FISH) with Cy3-conjugated PNA (peptide nucleic acid) oligonucleotide (CCCTAA)3 on peripheral blood metaphases was performed [6]. This analysis depicted telomere shortening in HHS lymphocytes comparing with normal lymphocytes (Fig. 2a,b). As a complementary cytogenetic evaluation, chromosome preparations were obtained from BM aspirate. Half of the metaphases analyzed by GTG-banding showed pseudodiploid complements with numerical changes and structural rearrangements in the form of non-clonal deletions. Chromatid breaks and a dicentric chromosome were also seen in three cells (Fig. 2c,d), while normal BM samples, obtained from pediatric cardiac surgery and cultivated under the same conditions, showed normal karyotype. Genomic instability has been previously shown in BM from a DKC patient, with translocations and ring chromosomes in more than 50% of cells [5]. A similar pattern of genomic instability has been previously associated with DKC but not with HHS. Our findings reinforce the presence of a high level of shared genetic background in both of theses rare conditions of childhood. A prospective international collaborative survey might be useful to

A systematic intervention for assistance of patients with asthma in Brazil: partnership between university and public health system

Methods A group of 16 allergists/immunologists developed a capacitating program in 11 Public Health Units in the city of Ribeirao Preto, Brazil. The program comprised lectures on asthma and hands-on training on spirometry and use of inhalation devices; production of didactic material; and development of a protocol on management of asthma. Spacers and spirometry were provided. Each researcher visited one Health Unit 2-4 times a month, to accompany the non-specialist on patients’ visits to the clinic, perform case discussions, and deliver short lectures to the health professionals. Records of asthma medications provided to patients upon physicians’ prescription in the North Region were compared to those from three other Regions with no intervention.

Allergy to cow's milk protein and reaction to methylprednisolone – case study

Conclusions Test performed with injectable methylprednisolone revealed the presence of nanograms of beta-lactoglobulin in the medication. The presence of food protein, intentionally or by contamination, in medications whose excipients are derived from food, makes the patients with food allergy, susceptible to present adverse reaction to the medication in question, although this occurrence is rare. Therefore patients with CMPA should be advised regarding the use of medications containing milk protein.

A male infant with eczema and persistent thrombocytopenia, without micro-platelets: an atypical Wiskott-Aldrich syndrome?

Background Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disorder characterized by early microthrombocytopenia, eczematous skin disease and recurrent infections. The syndrome is caused by mutations in gene WAS which codes WASP protein, that is expressed selectively in hematopoietic cells and it is involved in cell signaling and cytoskeleton reorganization. Microthrombocytopenia is the key hematological finding in patients with WAS. However, a normal mean platelet volume or the presence of giant platelets do not exclude a diagnosis of WAS.

DKC1 mutation causing different phenotypes in a family with X-linked Hoyeraal-Hreidarsson syndrome

Background Hoyeraal–Hreidarsson syndrome (HHS) is a rare multisystem disorder characterized by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, neurological deficits, aplastic anemia, and immunodeficiency. HHS is a severe variant of Dyskeratosis Congenita (DC) that displays clinical features overlapping DC, with T, B and NK immunodeficiency. Both genetic disorders presents deficiency in maintaining telomere integrity. Mutations in the DKC1 gene are responsible for the X-linked form of the disease.