There is no specific treatment for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a disease that is very rare in the pediatric population. We report the case of a 15-year-old boy who presented with mildly reduced kidney function and nephrotic syndrome. Kidney biopsy revealed PGNMID with monoclonal deposits of IgG3 with kappa light chain restriction. Flow cytometry showed a significant CD38 plasma cell population in the peripheral blood in the absence of other signs of hematological malignancy. The patient was treated with a 6-month course of daratumumab, a monoclonal antibody targeting CD38. There was a significant reduction in proteinuria and normalization of kidney function. Based on positive experience with adults, daratumumab should also be studied in children with PGNMID.
- MeSH
- antigeny CD38 imunologie analýza MeSH
- biopsie MeSH
- imunoglobulin G * krev MeSH
- ledviny patologie imunologie účinky léků MeSH
- lidé MeSH
- membranoproliferativní glomerulonefritida * farmakoterapie imunologie patologie MeSH
- mladiství MeSH
- monoklonální protilátky * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Monosomy 7 is the most common cytogenetic abnormality in pediatric myelodysplastic syndrome (MDS) and associated with a high risk of disease progression. However, in young children, spontaneous loss of monosomy 7 with concomitant hematologic recovery has been described, especially in the presence of germline mutations in SAMD9 and SAMD9L genes. Here, we report on our experience of close surveillance instead of upfront hematopoietic stem cell transplantation (HSCT) in seven patients diagnosed with SAMD9L syndrome and monosomy 7 at a median age of 0.6 years (range, 0.4-2.9). Within 14 months from diagnosis, three children experienced spontaneous hematological remission accompanied by a decrease in monosomy 7 clone size. Subclones with somatic SAMD9L mutations in cis were identified in five patients, three of whom attained hematological remission. Two patients acquired RUNX1 and EZH2 mutations during the observation period, of whom one progressed to myelodysplastic syndrome with excess of blasts (MDS-EB). Four patients underwent allogeneic HSCT at a median time of 26 months (range, 14-40) from diagnosis for MDSEB, necrotizing granulomatous lymphadenitis, persistent monosomy 7, and severe neutropenia. At last follow-up, six patients were alive, while one passed away due to transplant-related causes. These data confirm previous observations that monosomy 7 can be transient in young children with SAMD9L syndrome. However, they also indicate that delaying HSCT poses a substantial risk of severe infection and disease progression. Finally, surveillance of patients with SAMD9L syndrome and monosomy 7 is critical to define the evolving genetic landscape and to determine the appropriate timing of HSCT (clinicaltrials gov. Identifier: NCT00662090).
- MeSH
- chromozomální delece * MeSH
- dítě MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- kojenec MeSH
- lidé MeSH
- lidské chromozomy, pár 7 genetika MeSH
- monozomie MeSH
- myelodysplastické syndromy * diagnóza genetika terapie MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- spontánní remise MeSH
- transkripční faktory genetika MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
Paroxysmal cold hemoglobinuria (PCH) is a rare condition in childhood characterized by complement-mediated premature destruction of red blood cells. PCH is associated with intravascular hemolysis causing hemoglobinuria, which may result in acute kidney injury of various severity. We aimed to retrospectively analyze clinical and laboratory features of children with PCH-associated acute kidney injury received at tertiary Pediatric Hematology and Nephrology Center, University Motol Hospital, Prague, Czech Republic during the period 2016 to 2022. We present here 3 children with PCH-associated acute kidney failure requiring renal replacement therapy. We highlight the association of PCH with kidney disease. Renal parameters and urine examination should be regularly tested in all children with PCH.
- MeSH
- akutní poškození ledvin * komplikace MeSH
- dítě MeSH
- erytrocyty MeSH
- hemolýza MeSH
- lidé MeSH
- nízká teplota MeSH
- paroxysmální hemoglobinurie * komplikace diagnóza MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Schimke immunoosseous dysplasia (SIOD) is an ultra-rare inherited disease affecting many organ systems. Spondyloepiphyseal dysplasia, T-cell immunodeficiency and steroid resistant nephrotic syndrome are the main symptoms of this disease. CASE PRESENTATION: We aimed to characterize the clinical, pathological and genetic features of SIOD patients received at tertiary Pediatric Nephrology Center, University Hospital Motol, Prague, Czech Republic during the period 2001-2021. The mean age at diagnosis was 21 months (range 18-48 months). All patients presented with growth failure, nephropathy and immunodeficiency. Infections and neurologic complications were present in most of the affected children during the course of the disease. CONCLUSIONS: Although SIOD is a disease characterized by specific features, the individual phenotype may differ. Neurologic signs can severely affect the quality of life; the view on the management of SIOD is not uniform. Currently, new therapeutic methods are required.
- MeSH
- centra terciární péče MeSH
- kvalita života MeSH
- lidé MeSH
- nefrotický syndrom * diagnóza genetika komplikace MeSH
- osteochondrodysplazie * diagnóza genetika terapie MeSH
- syndromy imunologické nedostatečnosti * diagnóza genetika komplikace MeSH
- vzácné nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Česká republika MeSH
Hemofagocytující lymfohistiocytóza neboli HLH je heterogenní skupina onemocnění charakterizovaná nekontrolovatelnou aktivací a proliferací T lymfocytů a makrofágů, která vede k nadprodukci cytokinů a k hemofagocytóze v kostní dřeni a tkáních. Jedná se o stav, který bez adekvátní a včasné léčby ohrožuje pacienta na životě. V našem sdělení představujeme kazuistiku kojence, který byl u nás na klinice hospitalizován s rozvojem sekundární HLH při infekci virem SARS-CoV-2. Covid-19 přináší do medicíny celou řadu výzev, jednou z nich je i včasné rozpoznání vzácných komplikací, které pacientovi přináší.
Hemophagocytic lymphohistiocytosis (HLH) is heterogeneous disease characterized by uncotrolled proliferation of T lymphocytes and macrophages result of which is overproduction of cytokines and hemophagocytosis. Without adequate therapy this condition could be life-threatening. We present a case of infant with secondary hemophagocytic lymphohistiocytosis in SARS-CoV-2 infection.
- Klíčová slova
- hepatosplenomegalie,
- MeSH
- COVID-19 * komplikace MeSH
- kojenec MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * diagnóza etiologie terapie MeSH
- pancytopenie diagnóza etiologie MeSH
- výsledek terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Our study presents a novel germline c.1715G>T (p.G572V) mutation in the gene encoding Toll-like receptor 8 (TLR8) causing an autoimmune and autoinflammatory disorder in a family with monozygotic male twins, who suffer from severe autoimmune hemolytic anemia worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis, and CNS vasculitis. The pathogenicity of the mutation was confirmed by in vitro assays on transfected cell lines and primary cells. The p.G572V mutation causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling. This imbalance toward TLR7-dependent signaling leads to increased pro-inflammatory responses, such as nuclear factor-κB (NF-κB) activation and production of pro-inflammatory cytokines IL-1β, IL-6, and TNFα. This unique TLR8 mutation with partial TLR8 protein loss and hyperinflammatory phenotype mediated by TLR7 ligands represents a novel inborn error of immunity with childhood-onset and a good response to TLR7 inhibition.
- MeSH
- autoimunitní hemolytická anemie genetika imunologie MeSH
- cytokiny genetika imunologie MeSH
- dvojčata monozygotní MeSH
- HEK293 buňky MeSH
- lidé MeSH
- mutace * MeSH
- posouzení stavu pacienta MeSH
- toll-like receptor 7 genetika imunologie MeSH
- toll-like receptor 8 genetika imunologie MeSH
- zánět genetika imunologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- studie na dvojčatech MeSH
Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer. Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry. Whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) were employed to identify causative mutations in newly diagnosed patients and in cases with previously unrecognized molecular pathology. RP mutation detection rate was 81% (50/62 patients). This included 8 novel point mutations and 4 large deletions encompassing some of the RP genes. Malignant or predisposing condition developed in 8/62 patients (13%): myelodysplastic syndrome in 3 patients; breast cancer in 2 patients; colorectal cancer plus ocular tumor, diffuse large B-cell lymphoma and multiple myeloma each in one case. These patients exclusively harbored RPL5, RPL11 or RPS19 mutations. Array CGH is beneficial for detection of novel mutations in DBA due to its capacity to detect larger chromosomal aberrations. Despite the importance of genotype-phenotype correlation in DBA, phenotypic differences among family members harboring an identical mutation were observed.
- MeSH
- Diamondova-Blackfanova anemie komplikace epidemiologie genetika MeSH
- genetické asociační studie MeSH
- lidé MeSH
- mutace * MeSH
- nádory etiologie MeSH
- registrace MeSH
- ribozomální proteiny genetika MeSH
- rodina MeSH
- sekvenování exomu MeSH
- srovnávací genomová hybridizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
