RESUMO
The monogenic causes of very-early-onset inflammatory bowel disease (VEO-IBD) have been defined by genetic studies, which were usually related to primary immunodeficiencies. Receptor-interacting serine/threonine-protein kinase-1 (RIPK1) protein is an important signalling molecule in inflammation and cell death pathways. Its deficiency may lead to various clinical features linked to immunodeficiency and/or inflammation, including IBD. Here, we discuss an infant with malnutrition, VEO-IBD, recurrent infections and polyathritis who has a homozygous partial deletion in RIPK1 gene.
Assuntos
Deleção de Genes , Doenças Inflamatórias Intestinais , Proteína Serina-Treonina Quinases de Interação com Receptores , Humanos , Lactente , Masculino , Idade de Início , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/diagnóstico , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/deficiênciaRESUMO
BACKGROUND: Liver damage is uncommon in Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS). Herein, we present two cases with a diagnosis of STEC-HUS that progressed to liver damage, with findings presumably related to the SERPINB11 gene c.268G > T (p.Glu90Ter) variant. CASE-DIAGNOSIS/TREATMENT: Two boys aged 3 and 2 years, respectively, were referred to our clinic with a preliminary diagnosis of STEC-HUS. The patients had low hemoglobin, thrombocyte, and haptoglobin levels but high levels of lactic dehydrogenase, urea, creatinine, and schistocytes in peripheral smears. Escherichia coli O157:H7 was detected in their stool samples. The patients underwent hemodialysis, plasma exchange, and supportive treatments. Meanwhile, cholestasis developed in the patients, resulting in elevated total bilirubin levels. During the follow-up period, kidney function recovered completely; however, liver function did not improve, and one patient developed chronic liver damage. Gene mutations that may cause liver damage were investigated, and c.268G > T (p.Glu90Ter) homozygous and heterozygous variants were detected in exon 9 of the SERPINB11 gene in the patients. CONCLUSIONS: Our patients presented with kidney impairment and liver malfunction. Hepatic involvement in STEC-HUS may result from ischemia, hemolysis, and endothelial damage in the hepatic vessels. Liver injury in STEC-HUS cases may be associated with the homozygous SERPINB11 gene c.268G > T (p.Glu90Ter) variant.
Assuntos
Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Serpinas , Escherichia coli Shiga Toxigênica , Masculino , Humanos , Creatinina , Haptoglobinas , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/diagnóstico , Síndrome Hemolítico-Urêmica/complicações , Fígado , Ureia , Oxirredutases , Hemoglobinas , BilirrubinaRESUMO
Increased photosynthetic efficiencies in genotypes with greater proline level and in crops treated with proline under water deficit have been reported in recent years, but the biochemical and molecular mechanisms of this process are still not known. We examined photosystem II (PSII) activity, photosynthetic enzymes, ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco), phosphoenolpyruvate carboxylase (PEPc), rubisco activase (RCA), and chlorophyll metabolic enzymes, magnesium chelatase (Mg-CHLI), and chlorophyllase (Chlase), which would be the primary targets of exogenous proline to provide photosynthetic protection to plants under PEG-induced short-term water deficit. Two maize genotypes W23/M14 with greater proline content and Safak with low proline content were hydroponically grown for 21-23 days, and then the seedlings were subjected to water deficit (- 0.75 MPa) induced by PEG6000 for 0, 4, and 8 h. Before the seedlings were exposed to the water deficit, proline (1 mM) was applied to the rooting medium of the Safak genotype for 2 days. The time course effects of the applications showed that exogenous proline significantly enhanced PSII efficiency, PEPc activity, rubisco activity, and the relative expression levels of PEPc, rubisco large subunit, rubisco small subunit, and RCA genes at 0, 4, and 8 h. The W23/M14 genotype had higher rubisco quantity than the Safak genotype at all time periods. Proline pre-treatment under the stress-free and PEG conditions reduced the activity of Chlase and the gene expressions of Chlase, while it enhanced Mg-CHLI gene expression at 0, 4, and 8 h. Taken together, the results indicated that the primary target of proline-stimulated signaling in maize seedlings exposed to short-term severe water deficit may be to induce PSII efficiency, activities of carbon dioxide fixation enzymes and chlorophyll metabolism and mitigate chlorophyll degradation.
Assuntos
Clorofila/metabolismo , Fotossíntese/fisiologia , Prolina/metabolismo , Plântula/metabolismo , Zea mays/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Água/metabolismoRESUMO
BACKGROUND: The diagnosis of cows milk protein allergy (CMPA) is not always easy. Cow's Milk-related Symptom Score (CoMiSS) has been developed to raise the awareness of CMPA among the primary health-care providers. In this study, we aimed to evaluate the validity of CoMiSS as a diagnostic approach of CMPA in infants in our country. METHODS: Infants with a CoMiSS of more than 12 points were included. An elimination diet was implemented in these infants for 4 weeks, and CoMiSS was reapplied. Infants with a reduction of ≥3 points in CoMiSS were considered responsive to the elimination diet, and an open oral challenge test was performed. Infants with symptom recurrence were diagnosed with CMPA. RESULTS: The study included 168 infants. When they were included in the study, the first CoMiSS score was 13.6 ± 1.9. After the elimination diet, the number of responsive infants was 154 (91.7%). Of the infants, 91 (54.2%) were diagnosed with CMPA with positive challenge. The majority of the patients diagnosed with CMPA presented with gastrointestinal and/or dermatological symptoms (80.3%). Positive family history of allergy was more prevalent in CMPA(+) infants (P < 0.001). The mean atopic dermatitis score was higher in CMPA(+) infants (P = 0.001). Eosinophilia and cows milk-specific IgE (CM-sIgE) positivity were more prevalent in infants with CMPA (P = 0.01 and P < 0.001, respectively). CONCLUSIONS: CoMiSS is a valuable tool to evaluate CMPA in primary care. The presence of multiple symptoms, especially skin involvement, helps to recognise infants with CMPA. Family history and eosinophilia also support the diagnosis of CMPA.
Assuntos
Hipersensibilidade a Leite , Leite , Alérgenos , Animais , Bovinos , Criança , Feminino , Humanos , Imunoglobulina E , Lactente , Hipersensibilidade a Leite/diagnóstico , Proteínas do Leite , RecidivaRESUMO
DOCK8 deficiency is a rare inherited combined immunodeficiency, caused by mutations in the DOCK8 gene. We describe a case with DOCK8 deficiency associated with severe CLD in whom orthotopic LT was performed successfully after allogeneic HSCT. A 5 year-old girl with DOCK8 deficiency presented with mild direct hyperbilirubinemia and abnormal GGT level and without a previous history of jaundice. She had severe growth retardation, hepatosplenomegaly and generalized eczema. Progressive worsening of CLD was observed within 4 months. Investigations for etiology of liver disease were negative. Liver biopsy showed bridging necrosis, cholestasis and, cirrhosis. Recurrent immune hemolytic crisis and several viral infections developed in follow-up. She underwent whole cadaveric LT for end-stage liver disease (ESLD) 1 year after allogenic HSCT from a full matched related donor. The postoperative course was uneventful. The patient is alive with normal liver function and moderate skin graft versus host disease for 36 months after LT. In conclusion DOCK8 deficiency can be associated with severe CLD. Successful LT following HSCT is possible in patients with ESLD in DOCK8 deficiency. The timing of LT is challenging in patients requiring both HSCT and LT since conditioning regimens for HSCT can be highly hepatotoxic and the patients with suboptimal liver function can become decompensated during HSCT.
Assuntos
Colestase Intra-Hepática/terapia , Fatores de Troca do Nucleotídeo Guanina/deficiência , Transplante de Células-Tronco Hematopoéticas , Transplante de Fígado , Imunodeficiência Combinada Severa/terapia , Biomarcadores/metabolismo , Pré-Escolar , Colestase Intra-Hepática/etiologia , Terapia Combinada , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Mutação , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/metabolismoRESUMO
Chronic cough in children may be due to a diverse range of etiologies. We aimed to evaluate children with chronic cough following a standardized cough algorithm and assess obstructive sleep apnea (OSA) as a possible etiology. In addition, cough resolution rates of two different treatment protocols in children with non-specific cough were compared. A total of 237 children referred for chronic cough were assessed and classified according to etiologies. Children with non-specific cough were assigned either in the early-arm (group-1, n = 13) or delayed arm (group-2, n = 23). The presence of OSA was evaluated using a pediatric sleep questionnaire, and polysomnography was handled in indicated patients. Asthma (n = 82) and protracted bacterial bronchitis (PBB) (n = 73) were the most frequent etiologies. Cough resolution was higher in group-1 (100%) compared with group-2 (50%) (absolute risk reduction (rr) = 43.48% [95% CI 21.38-65.58%]). Polysomnography revealed mild (n = 6), moderate (n = 7), or severe (n = 5) OSA in 18 children, with adenoid/adenotonsillary hypertrophy as the leading cause.Conclusion: We recognized asthma and PBB as the most frequent causes of chronic cough in our cohort. Early treatment of patients with high parental anxiety might be beneficial. We also believe that further studies including larger series might eventuate in incorporation of assessment of OSA to standardized algorithms. What is known? ⢠Chronic cough in children may be due to a diverse range of etiologies, including serious respiratory disorders. Thus, its correct diagnosis and treatment are essential. ⢠Although a well-defined reason of chronic cough in adults, obstructive sleep apnea (OSA) has not been been evaluated so far in children with chronic cough. What is new? ⢠We examined OSA for the first time as a possible cause of chronic cough in children and detected OSA with polysomnography in cases who scored high pediatric sleep questionnaire (PSQ) scores. ⢠We believe that studies including larger series might eventuate in incorporation of assessment of OSA to standardized algorithms for children with chronic cough.
Assuntos
Tosse/etiologia , Apneia Obstrutiva do Sono/diagnóstico , Adolescente , Algoritmos , Criança , Pré-Escolar , Doença Crônica , Estudos de Coortes , Tosse/tratamento farmacológico , Feminino , Seguimentos , Humanos , Lactente , Masculino , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia , Inquéritos e QuestionáriosRESUMO
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a well-known mitochondrial depletion syndrome. Since Van Goethem et al. described MNGIE syndrome with pathogenic POLG1 mutations in 2003, POLG1 gene became a target for MNGIE patients. Cases with POLG1 mutations strikingly differ from classic MNGIE patients due to a lack of leukoencephalopathy. Here we present a female patient with very early onset disease and leukoencephalopathy compatible with classic MNGIE disease who turned out to have homozygous POLG1 mutation compatible with MNGIE-like syndrome, mitochondrial depletion syndrome type 4b.
Assuntos
Leucoencefalopatias , Encefalomiopatias Mitocondriais , Humanos , Feminino , Encefalomiopatias Mitocondriais/complicações , Encefalomiopatias Mitocondriais/genética , Encefalomiopatias Mitocondriais/patologia , Timidina Fosforilase/genética , Mutação/genética , Leucoencefalopatias/genética , Leucoencefalopatias/complicações , SíndromeRESUMO
Congenital sucrase-isomaltase deficiency (CSID) is a rare autosomal carbohydrate malabsorption disorder caused by mutations in the sucrase-isomaltase gene. While the prevalence of CSID is high in the indigenous populations of Alaska and Greenland, it is imprecise and ambiguous in the Turkish pediatric population. In this cross-sectional case-control study, which is retrospective in nature, next-generation sequencing (NGS) results obtained from records of 94 pediatric patients with chronic nonspecific diarrhea were reviewed. Demographic characteristics, clinical symptoms and treatment responses of those diagnosed with CSID were evaluated. We identified one new, homozygous frame-shift mutation and 10 other heterozygous mutations. Two cases were from the same family and nine were from different families. While the median age at onset of symptoms was 6 months (0-12), median age at diagnosis was 60 months (18-192) with a median delay of 5 years and 5 months (10 months -15 years and 5 months) in diagnosis. Clinical symptoms included diarrhea (100%), abdominal pain (54.5%), vomiting after consuming sucrose (27.2%), diaper dermatitis (36.3%) and growth retardation (81%). Our clinical study revealed that sucrase-isomaltase deficiency may have been underdiagnosed in patients with chronic diarrhea in Turkey. In addition, the frequency of heterozygous mutation carriers was significantly higher than that of homozygous mutation carriers and those with a heterozygous mutations responded well to the treatment.
Assuntos
Diarreia , Criança , Humanos , Lactente , Recém-Nascido , Estudos de Casos e Controles , Estudos Transversais , Diarreia/epidemiologia , Diarreia/genética , Prevalência , Estudos Retrospectivos , Turquia/epidemiologia , Complexo Sacarase-Isomaltase/metabolismoRESUMO
OBJECTIVES: To assess the effects of a gluten-free diet on bone structure in children with celiac disease using fractal analysis on panoramic radiographs. METHOD AND MATERIALS: A total of 49 patients with celiac disease aged 6 to 13 years, separated into two groups as previously and newly diagnosed, and a control group of 32 healthy individuals were evaluated. In previously and newly diagnosed patients with celiac disease, body mass index Z-scores were calculated, calcium, alkaline phosphatase, vitamin D3, and parathormone levels were measured, and bone mineral density Z-scores were obtained from dual energy x-ray absorptiometry. In all patients, the fractal dimensions of the right and left temporomandibular condyles were evaluated with the fractal analysis method on panoramic radiographs. RESULTS: The mean values of serum biomarker levels and the body mass index and bone mineral density Z-scores for both celiac groups were within the normal reference range. No statistically significant difference was determined between right and left condyle fractal dimensions values in the three groups examined. In terms of both right and left condyle fractal dimensions values, there was a statistically significant difference between groups. The highest fractal dimensions values were determined in the previously diagnosed group. CONCLUSIONS: Differences in fractal dimensions values were observed among patients with celiac disease following the gluten-free diet. Utilizing fractal analysis on panoramic radiographs can prove valuable for dental practitioners in evaluating bone mineral density due to its cost-effectiveness, easy accessibility, and reduced radiation exposure for patients, enabling them to provide comprehensive oral health care and potential early interventions for patients with celiac disease.
Assuntos
Doença Celíaca , Criança , Humanos , Doença Celíaca/diagnóstico por imagem , Densidade Óssea , Fractais , Odontólogos , Papel Profissional , Osso e Ossos , Radiografia PanorâmicaRESUMO
Protective compounds such as non-enzymatic antioxidants, osmolytes and signal molecules have been applied to plants exposed to various environmental stresses to increase their stress tolerance. However, there are not enough records about the response of plants to alpha lipoic acid (ALA) application with antioxidant properties. Therefore, this study was designed to evaluate the function of exogenous ALA on the photosynthetic performance of maize seedlings grown in hydroponic conditions under drought stress. Three weeks old seedlings were treated with or without ALA (12 µM) and they were subjected to drought stress induced by 10% polyethylene glycol (PEG6000) for 24 h. Chlorophyll content, gas exchange parameters, chlorophyll fluorescence and the expression levels of genes involved in CO2 fixation (ribulose-1,5-bisphosphate carboxylase (rubisco), phosphoenolpyruvate carboxylase (PEPc), Rubisco activase (RCA)) and chlorophyll metabolism (magnesium chelatase (Mg-CHLI) and chlorophyllase (Chlase)) were determined. The application of ALA increased chlorophyll content and the activity of photosystem II in comparison to the untreated seedlings under drought stress. The relative expression levels of Rubisco, PEPc, RCA and Mg-CHLI significantly increased while the Chlase gene expression decreased in seedlings to which ALA was applied in comparison those to which it was not applied under the stress. These results suggest that exogenous ALA can enhance the photosynthetic performance of maize seedlings exposed to drought by inducing photosystem II activity and the gene expressions of carbon fixation and chlorophyll metabolism enzymes.
Assuntos
Ciclo do Carbono/efeitos dos fármacos , Clorofila/metabolismo , Complexo de Proteína do Fotossistema II/efeitos dos fármacos , Plântula/efeitos dos fármacos , Ácido Tióctico/farmacologia , Zea mays/efeitos dos fármacos , Western Blotting , Desidratação , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Plântula/enzimologia , Plântula/metabolismo , Zea mays/enzimologia , Zea mays/metabolismoRESUMO
OBJECTIVES AND STUDY: Failure to thrive (FTT) is an interruption in the normal pattern of growth. We aimed to evaluate the clinical characteristics, underlying etiologies, diagnostic workup, and frequency of micronutrient deficiencies (MDs) in children with FTT. METHODS: This retrospective study was done with 729 children (319 male, mean age 6.8 ± 5.5 years) with FTT (weight for age <3rd percentile) who had visited the Pediatric Gastroenterology outpatient clinic between 2011 and 2016. Children who had previously known chronic diseases, inadequate intake, or inadequate absorption were excluded. Acute malnutrition was considered if weight-for-age z-scores were below -2 and height-for-age z-scores were above -2, and chronic malnutrition was defined if height-for-age z-scores were below -2. RESULTS: The malnutrition rate was 57.1% (acute: 37.8%, chronic: 19.3%). Of children, 98.7% had laboratory evaluation. We found that 1.1% of laboratory tests, 0.4% of imaging studies, 27% of endoscopic findings, and biopsy results led to a specific diagnosis, equating to a total of 1.3% of diagnostic workup leading to a diagnosis related to FTT. The causes of FTT were inadequate nutrition (61.4%), psychiatric and behavioral disorders (17.2%), endocrinologic disorders (9%), recurrent infections (6.4%), gastrointestinal diseases (1.9%), and cardiac disorders (0.1%). Vitamin A and D deficiencies were the most common MD. CONCLUSION: We showed that the most common cause of FTT is "purely nutrition" FFT because of inadequate caloric intake, and extensive diagnostic workup is rarely helpful to reveal the etiology. These results implicate the importance of clinical evaluation and anthropometry to evaluate a child with FTT.