Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5-14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (NARS1 and DCAF5). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

WstępDefinicja wrodzonej wady rozwojowej jest bardzo szeroka i obejmuje każdą nieprawidłowość anatomiczną obecną przy urodzeniu. Wady wrodzone stwierdza się u około 2-3% żywo urodzonych noworodków, wśród martwo urodzonych do 10%, natomiast ponad 50% płodów z ciężkimi wadami rozwojowymi ulega obumarciu i poronieniu we wczesnym okresie trwania ciąży [1,2]. Etiologia wrodzonych wad p e d i a t r i a p o l s k a 8 9 ( 2 0 1 4 ) 3 8 9 -3 9 4

Introduction: Bone marrow transplantation (BMT) from HLA identical family donors is the treatment chosen for children with (SAA). When no donor is available, combined immunosuppressive therapy (IS) is given. Material and method: SAA was recognised in 85 children (31 girls, 54 boys) aged 2–17.5 years in ten haematological clinic in Poland between 1993–2003 years. All patients received IS according SAA Working Party of the EBMT protocol: ALG or ATG, CsA, prenisolon and in 79 patients G-CSF or GM-CSF was additionally administered. Haematological response was evaluated on day 180 of therapy. Results and conclusion: Complete remission (CR) occurred in 43 patients (40.5%), partial remission (PR) on 22 (25.8%), no response (NR) was obtained in 20 children (23.7%). Period of observation was from 12 months to 10.5 years. During this time relapse occurred in 10 patients (8.5%). Patients with NR and relapse were treated second course of IS or BMT from matched bone marrow donors. Unrelated BMT was performed in 11 patients with NR after IS. We observed 17 deaths (10 early during the first 3 months of IS) in all group. At present 54 children (63.5%) is in first remission (CR or PR) with lasts from 12 months to 10 years. During the 10.5 year of observation we notice one case with late clonal complication (PNH). Transformation to neoplasma was not observed in none of our patients after IS.