Agata Skórka

Meta‐analysis: Lactobacillus GG for treating acute diarrhoea in children

Aim To review evidence for the effectiveness of Lactobacillus GG (LGG) in treating acute infectious diarrhoea in children.

Meta-analysis : Saccharomyces boulardii for treating acute diarrhoea in children

Saccharomyces boulardii is a non‐pathogenic probiotic yeast considered useful against enteropathogens.

Lymphoid tyrosine phosphatase (PTPN22/LYP) variant and Graves' disease in a Polish population: association and gene dose-dependent correlation with age of onset.

Objective  Susceptibility to Graves’ disease (GD) is to a significant extent determined by genetic factors of which the best known are those associated with the HLA and the CTLA4 locus. Recently, two studies on British Caucasians reported that a single nucleotide polymorphism, 1858 C>T in PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which is a negative regulator of T‐cell activation, increases the risk of GD. The purpose of our study was to investigate whether the PTPN22‘T’ allele is associated with GD and/or its subsets, defined by clinical or genetic parameters, in a Polish population.

M34T and V37I mutations in GJB2 associated hearing impairment: Evidence for pathogenicity and reduced penetrance

Despite research the role of the M34T and V37I variants of GJB2 in causing hearing impairment (HI) remains controversial. Our purpose was to test a hypothesis that M34T and V37I are pathogenic but have distinct features resulting in a reduced penetrance. We screened for known GJB2/GJB6 mutations 233 Polish consecutive unrelated subjects with non‐syndromic, sensorineural HI who were previously found to carry 35delG mutation on one chromosome. The most frequent mutations were also analyzed in ∼1,000 controls. We found that M34T and V37I were significantly (P ≪ 10−6) overrepresented among patients, but their penetrance was estimated as 1/10 relative to mutations of undisputed pathogenicity. This finding apparently could not be explained by low degree of HI associated with M34T and V37I since another mutation causing comparably mild HI (L90P) did not have reduced penetrance. Subsequent analyses showed that the patients with M34T/35delG and V37I/35delG had significantly later onset of HI than patients with other genotypes (P < 10−6) including the L90P/35delG (P = 0.006). Also, among these patients (but not others) a strong correlation between the degree of HI and its duration was found (r = 0.79, P < 10−5). We tentatively suggest that M34T and V37I might cause mild HI characterized by relatively late onset and progression.

Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children – updated analysis of randomised controlled trials

The efficacy of each probiotic should be evaluated separately. Previously, we have shown that Lactobacillus GG (LGG) is effective in treating acute gastroenteritis (AGE) in children.

Saccharomyces boulardii for treating acute gastroenteritis in children: updated meta-analysis of randomized controlled trials

SIRS, Previously, we have shown in a meta-analysis that Saccharomyces boulardii, a nonpathogenic probiotic yeast, is effective in treating acute gastroenteritis (AGE) in children. A number of studies have been published since this meta-analysis, some with negative results, prompting interest in re-evaluating the role of S. boulardii in the management of AGE. This letter summarizes the updated results from trials of S. boulardii performed in children with AGE. The methods used in this meta-analysis are discussed in full detail in the original version of this review. In brief, the MEDLINE, EMBASE and the Cochrane Library databases, as well as major paediatric conference proceedings were searched from August 2006 (end date of last search) to August 2009. The pharmaceutical company, Biocodex (France) that manufactures S. boulardii was contacted to help identify published and unpublished data. The updated meta-analysis included nine randomized controlled trials (RCTs) involving 1117 participants compared with five RCTs (619 participants) included in the original analysis. Overall, five studies were placebocontrolled. In the remaining trials, there was no additional intervention in the control group. The ages of the participants varied from 2 months to 12 years. The daily dose of the study product ranged from 250–750 mg. The duration of the intervention ranged from 5–7 days. The methodological quality of the trials varied. Tables with the updated characteristics of included and excluded trials are available upon request. A meta-analysis of seven RCTs 7, 9, 10 (944 participants) showed a reduction in the duration of the diarrhoea (weighted mean difference )1.08 day, 95% CI )1.64 to )0.53, random effects model) in those treated with S. boulardii compared with placebo (Figure 1). In conclusion, this update of our meta-analysis of data from RCTs confirms that in otherwise healthy infants and children, the use of S. boulardii is associated with clinical benefits in the treatment of AGE, specifically a reduction in the duration of diarrhoea by approximately 1 day. As before, these findings should be interpreted with caution because of the methodological limitations and heterogeneity of some of the studies. The available evidence supports recent recommendations from two European societies that selected probiotics with proven clinical efficacy, such as S. boulardii or Lactobacillus GG that are administered in appropriate dosages, according to the strain and the patient population, may be used as an adjunct to rehydration therapy for the management of AGE in children. 9 Moore A, Bjarnason I, Cryer B, et al. Evidence for Endoscopic Ulcers as Meaningful Surrogate Endpoint for Clinically Significant Upper Gastrointestinal Harm. Clin Gastroenterol Hepatol. 2009. Apr 9. [Epub ahead of print] 10 Yeomans N, Lanas A, Labenz J, et al. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol 2008; 103: 2465–73. 11 Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 2004; 127: 1038–43.

Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence.

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is an autosomal‐recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estimate disease prevalence. While studying 14 unrelated patients, we identified three novel mutations (c.1A>T, affecting the start codon; [IVS1 + 1G>C; IVS1 + 5delG], a complex mutation affecting splice site; c. 908G>C, p.R303P, a missense mutation in plant homeodomain (PHD) and three previously reported mutations (c.769C>T, p.R257X; c.967_979del13bp, C322fsX372; c.931delT, p.C311fsX376). Eleven patients had mutations on both chromosomes, whereas in three patients only a single alteration with proven or likely pathogenic effect was detected. The most frequent was the p.R257X mutation (71% of chromosomes); its carriage rate was assessed in the background population. Analysis of 2008 samples showed eight heterozygotes, indicating the frequency of 0.40% (1:250) and the disease prevalence – 1:129,000 (95% confidence interval: 1:555,000 to 1:30,000). Comparison with an epidemiological estimate (1:619,000, derived for women) suggested that in Poland, APECED is underdiagnosed. Among the patients, no genotype/phenotype correlations were found, but we noted that women had earlier onset of hypoparathyroidism (p < 0.02) and were younger at diagnosis (p < 0.05) than men.

The risk factors of ketoacidosis in children with newly diagnosed type 1 diabetes mellitus

Szypowska A, Skórka A. The risk factors of ketoacidosis in children with newly diagnosed type 1 diabetes mellitus.

GJB2 and hearing impairment: promoter defects do not explain the excess of monoallelic mutations

The report by Matos et al 1 brings up an issue of an excessive frequency of patients with hearing impairment (HI) in whom only monoallelic GJB2 mutations are identified by commonly used testing strategies. Interestingly, Matos et al suggest that these patients could harbour mutations in promoter of GJB2 which therefore should be included in the routine screening.1 This conclusion was supported by a novel sequence variant (−3438T→C) affecting GJB2 promoter function and found in a Portuguese patient in trans with a coding region mutation.1 The relatively high frequency of genotypes with monoallelic GJB2 mutations, such as the 35delG mutation, among the patients has indeed been noted previously2 3 although the exact size of this effect in relation to the generally high frequency of 35delG in Caucasians (carrier rates reaching 4%)4 has not been estimated. Although screening of promoter regions is clearly an attractive option in patients with monoallelic GJB2 defects, before it can be included in routine testing it should be shown that the −3438T→C or similar alteration(s) do indeed occur with an appreciable frequency. Given the report of Matos et al ,1 we were interested to find out: (1) whether there is an excess of monoallelic GJB2 mutations among patients with HI from our centre and if so, what is its magnitude, and (2) what is the frequency of GJB2 promoter mutations such as −3438T→C among such patients. Owing to the high frequency …

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith–Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith–Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.