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1.
Artigo em Inglês | MEDLINE | ID: mdl-32740538

RESUMO

OBJECTIVES: Crohn disease (CD) can affect patient's quality of life (QOL) with physical, social, and psychological impacts. This study aimed to investigate the QOL of children with CD and its relationship with patient and disease characteristics. METHODS: Children ages from 10 to 17 years with diagnosed CD for more than 6 months were eligible to this cross-sectional study conducted in 35 French pediatric centers. QOL was assessed by the IMPACT-III questionnaire. Patient and disease characteristics were collected. RESULTS: A total of 218 children (42% of girls) were included at a median age of 14 years (interquartile range [IQR]: 13--16). Median duration of CD was 3.2 years (IQR: 1.7-5.1) and 63% of children were in clinical remission assessed by wPCDAI. Total IMPACT-III score was 62.8 (±11.0). The lowest score was in "emotional functioning" subdomain (mean: 42.8 ±â€Š11.2). Clinical remission was the main independent factor associated with QOL of children with CD (5.74 points higher compared with those "with active disease", 95% confidence interval [CI] 2.77--8.70, P < 0.001). Age of patient at the evaluation was found negatively correlated with QOL (-0.76 per year, 95% CI: -1.47 to -0.06, P = 0.009). Presence of psychological disorders was associated with a lower QOL (-9.6 points lower to those without, 95% CI: -13.34 to -5.86, P < 0.0001). Total IMPACT-III and its subdomains scores were not related to sex, disease duration, or treatments. CONCLUSIONS: These results not only confirm that clinical remission is a major issue for the QOL of patients, but also highlights the importance of psychological care.

2.
Endosc Int Open ; 8(7): E969-E973, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32617400

RESUMO

Background and study aims The real burden of urgent endoscopy in children has not been studied yet. Our aim was to evaluate the need for urgent endoscopy in children. Patients and methods Information was collected about all the calls that were received during the 24 hour on-call shift for pediatric endoscopy in the region of Ile-de-France (12.1 million inhabitants) during a 6 months period (February-July 2017). Results A total of 237 calls (19 calls/y/100,000 children) were collected regarding children of an average age of 3.2 years (range 2 days-18 years). Most of the calls (68 %) were for foreign body ingestions. Gastroscopy was required in 32 % of children: 24 % of those calling for foreign body ingestion, 48 % for gastrointestinal bleeding, 63 % for caustic ingestions ( P  = 0.01). The average time between the call and the urgent endoscopy were below the international recommendations for each situation. Conclusions Calling the endoscopist seems to have become a recurrent practice, although in most cases, urgent endoscopy did not appear necessary, especially for foreign body ingestion. This organization of pediatric endoscopy on call was able to guarantee the performance of urgent endoscopy in adequate timing for a highly populated region.

4.
Front Immunol ; 10: 2592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787977

RESUMO

Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene cause very early onset inflammatory bowel diseases (VOIBD) or multiple intestinal atresia associated with immune deficiency of various severities, ranging from combined immune deficiency to mild lymphopenia. In this manuscript, we report the clinical, biological and molecular features of a patient born from consanguineous parents, presenting with recurrent lymphoproliferative syndrome and pan-hypergammaglobulinemia associated with chronic intestinal pseudo obstruction (CIPO). Genetic screening revealed the novel c.974G>A (p.R325Q) mutation in homozygosity in the TTC7A gene. The patient's phenotype differs significantly from that previously associated with TTC7A deficiency in humans. It becomes closer to the one reported in the ttc7a-deficient mice that invariably develop a proliferative lymphoid and myeloid disorder. Functional studies showed that the extreme variability in the clinical phenotype couldn't be explained by the cellular phenotype. Indeed, the patient's TTC7A mutation, as well as the murine-ttc7 mutant, have the same functional impact on protein expression, DNA instability and chromatin compaction, as the other mutations that lead to classical TTC7A-associated phenotypes. Co-inheritance of genetic variants may also contribute to the unique nature of the patient's phenotype. The present case report shows that the clinical spectrum of TTC7A deficiency is much broader than previously suspected. Our findings should alert the physicians to consider screening of TTC7A mutations in patients with lymphoproliferative syndrome and hypergammaglobulinemia and/or chronic intestinal pseudo-obstruction.


Assuntos
Pseudo-Obstrução Intestinal/etiologia , Transtornos Linfoproliferativos/etiologia , Deficiência de Proteína , Proteínas/fisiologia , Animais , Células Cultivadas , Doença Crônica , Consanguinidade , Feminino , Humanos , Lactente , Pseudo-Obstrução Intestinal/genética , Transtornos Linfoproliferativos/genética , Masculino , Camundongos , Proteínas/genética
5.
J Pediatr Gastroenterol Nutr ; 69(5): 528-532, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31436711

RESUMO

OBJECTIVES: Research on long-term use of mitomycin C (MC) for recurrent esophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent esophageal stenoses in children. METHODS: This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4-196.0) at the time of MC application. The etiologies of stenosis were esophageal atresia (n = 25), caustic ingestion (n = 9), congenital esophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child [range: 2-26]) over a median period of 7 months (range: 2.6-49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC. RESULTS: For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years [range: 0.6-8.5]). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and esophageal atresia type III. CONCLUSIONS: This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent esophageal stenosis in children.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Estenose Esofágica/tratamento farmacológico , Mitomicina/uso terapêutico , Administração através da Mucosa , Adolescente , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Esofagoscopia , Feminino , Humanos , Lactente , Masculino , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Complicações Pós-Operatórias , Estudos Retrospectivos
6.
J Pediatr ; 210: 161-165, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31053349

RESUMO

OBJECTIVES: To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia. STUDY DESIGN: A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels <160 mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development. RESULTS: The median duration of treatment with statins was 4 years. A median decrease of 32% in LDL-C levels was observed (P < .0001). The therapeutic target (LDL-C <160 mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment. CONCLUSIONS: The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Dor Abdominal/induzido quimicamente , Adolescente , Criança , LDL-Colesterol/sangue , Creatina Quinase/sangue , Disuria/induzido quimicamente , Feminino , Humanos , Masculino , Mialgia/induzido quimicamente , Dor/induzido quimicamente , Estudos Prospectivos
7.
Rev Prat ; 69(9): 1001-1004, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-32237625

RESUMO

Familial hypercholesterolemia in children and adolescents. Familial hypercholesterolemia is a common genetic disease. The dominant autosomal heterozygous form is most common in relation to the pathogenic mutation of a single gene responsible for a significant rise in LDL-cholesterol levels in childhood. In the absence of treatment, this abnormality exposes to a risk of early cardiovascular diseases in men and women. This pathology is totally asymptomatic in childhood. A lipid check-up should be proposed in case of a familial history of early cardiovascular diseases or severe dyslipidemia, if a mutation is already known in parents or if familial history is unknown. The diagnosis is suspected if LDL-cholesterol is > 1,6 g/L. A genetic assessment will be proposed according to family history and evolution. Management begins in childhood with the initial introduction of specific dietary measures. However, these are often insufficient requiring statin therapy from the age of 8.


Assuntos
Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Adolescente , Doenças Cardiovasculares/etiologia , Criança , LDL-Colesterol , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Mutação
9.
Front Immunol ; 9: 1036, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868001

RESUMO

The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37, two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects. First, switched memory B lymphocytes count is very low. Second, IFN-γ production by T and NK cells is impaired and associated with a reduced degranulation of NK cells. Third, T cell proliferation was abnormal in 3/6 TTC37-mutated patients. These three patients present with severe EBV infection and a transient hemophagocytosis which may be related to these immunological defects. Moreover, an immunological screening of patients with clinical features of SD/THE could facilitate both diagnosis and therapeutic management of these patients.


Assuntos
Linfócitos B/imunologia , Diarreia Infantil/complicações , Doenças do Cabelo/complicações , Síndromes de Imunodeficiência/etiologia , Células Matadoras Naturais/imunologia , Proteínas de Transporte/genética , Estudos de Coortes , DNA Helicases/genética , Diarreia Infantil/imunologia , Facies , Retardo do Crescimento Fetal/imunologia , Doenças do Cabelo/imunologia , Humanos , Síndromes de Imunodeficiência/genética , Memória Imunológica , Lactente , Recém-Nascido , Interferon gama/imunologia , Células Matadoras Naturais/patologia , Contagem de Linfócitos , Mutação , Linfócitos T/imunologia
10.
Nat Commun ; 8: 13998, 2017 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-28084299

RESUMO

Monolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture.


Assuntos
Células Epiteliais/química , Epitélio/química , Actomiosina/química , Actomiosina/genética , Actomiosina/metabolismo , Adolescente , Fenômenos Biomecânicos , Células CACO-2 , Polaridade Celular , Criança , Pré-Escolar , Diarreia Infantil/genética , Diarreia Infantil/metabolismo , Enterócitos/química , Enterócitos/metabolismo , Molécula de Adesão da Célula Epitelial/química , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Epitélio/metabolismo , Feminino , Humanos , Lactente , Síndromes de Malabsorção/genética , Síndromes de Malabsorção/metabolismo , Masculino , Junções Íntimas/química , Junções Íntimas/genética , Junções Íntimas/metabolismo
12.
J Pediatr Gastroenterol Nutr ; 64(1): 37-41, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28027214

RESUMO

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) (inflammatory bowel disease [IBD] before 6 years of age) may manifest as a monogenic disease affecting the gastrointestinal tract. Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE), a rare disorder caused by alteration of a complex involved in RNA degradation, has been reported to present with some degree of colitis and in some cases an IBD-like presentation. METHODS: We reviewed clinical and biological data of 4 previously published cases and added detailed data of 2 new cases of SD/THE with an IBD-like presentation. RESULTS: All the 6 patients presented with typical intractable diarrhea and hair abnormalities. The colon was affected in all of the patients: 1 had ileitis, 2 had panenteritis, and 2 presented with perianal disease. Fecal calprotectin level and erythrosedimentation rate were elevated in 2 cases each. All the therapeutic classes of IBD treatment (mesalazine, steroids, immunomodulators, and biological therapy) were used in the 6 cases. In 2 patients, treatment had no effect. Three showed a partial effect, and 1 patient sustained only a transient effect. CONCLUSIONS: SD/THE can have a similar presentation as VEOIBD, often as pancolitis. IBD treatments appear to have little efficacy for SD/THE, suggesting a different pathogenesis for the IBD-like features in SD/THE compared with classical IBD.


Assuntos
Colo/patologia , Diarreia Infantil/patologia , Retardo do Crescimento Fetal/patologia , Gastroenterite/etiologia , Doenças do Cabelo/patologia , Doenças Inflamatórias Intestinais/patologia , Intestino Delgado/patologia , Complexo Antígeno L1 Leucocitário/metabolismo , Anti-Inflamatórios/uso terapêutico , Terapia Biológica , Colite/etiologia , Diarreia/etiologia , Diarreia Infantil/tratamento farmacológico , Diarreia Infantil/metabolismo , Diarreia Infantil/terapia , Facies , Fezes/química , Feminino , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/terapia , Cabelo , Doenças do Cabelo/tratamento farmacológico , Doenças do Cabelo/metabolismo , Doenças do Cabelo/terapia , Humanos , Ileíte/etiologia , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Mesalamina/uso terapêutico , Síndrome
15.
J Allergy Clin Immunol ; 134(6): 1354-1364.e6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25174867

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases, but the underlying molecular mechanisms remain largely unknown. Studies of monogenic diseases can provide insight into the pathogenesis of IBD. OBJECTIVE: We thought to determine the underlying molecular causes of IBD occurring in 2 unrelated families in association with an immune deficiency. METHODS: We performed genetic linkage analysis and candidate gene sequencing on 13 patients from a large consanguineous family affected by early-onset IBD, progressive immune deficiency, and, in some cases, autoimmunity and alopecia, a condition we named enteropathy-lymphocytopenia-alopecia. The candidate gene was also sequenced in an unrelated patient with a similar phenotype. We performed histologic analysis of patients' intestinal biopsy specimens and carried out functional assays on PBMCs. Gut organoids derived from a patient's biopsy specimen were analyzed. RESULTS: We identified biallelic missense mutations in tetratricopeptide repeat domain 7A (TTC7A) in all patients from both families. The resulting TTC7A depletion modified the proliferation, adhesion, and migratory capacities of lymphocytes through inappropriate activation of the RhoA signaling pathway. Normal function was restored by wild-type TTC7A expression or addition of a RhoA kinase inhibitor. The growth and polarity of gut epithelial organoids were also found to be dependent on the RhoA signaling pathway. CONCLUSIONS: We show that TTC7A regulates the actin cytoskeleton dynamics in lymphocytes through the RhoA signaling pathway and is required in both lymphocytes and epithelial cells for maintaining equilibrium between cell proliferation, migration, polarization, and cell death. Our study highlights variability in the phenotypic expression resulting from TTC7A deficiency and outlines that impairment of both epithelial cells and lymphocytes cooperatively causes IBD.


Assuntos
Alopecia , Doenças Inflamatórias Intestinais , Linfopenia , Proteínas/genética , Proteínas/imunologia , Adolescente , Adulto , Alopecia/genética , Alopecia/imunologia , Alopecia/patologia , Criança , Pré-Escolar , Colo/patologia , Duodeno/patologia , Feminino , Humanos , Lactente , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Linfopenia/genética , Linfopenia/imunologia , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Antro Pilórico/patologia , Adulto Jovem , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/imunologia , Proteína rhoA de Ligação ao GTP/imunologia
16.
Arch Dis Child ; 99(1): 35-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24108068

RESUMO

OBJECTIVES: Syndromic diarrhoea/tricho-hepato-enteric syndrome (SD/THE) is a rare congenital syndrome. The main features are intractable diarrhoea of infancy, hair abnormalities, facial dysmorphism, intrauterine growth restriction and immune system abnormalities. It has been linked to abnormalities in two components of the putative human ski complex: SKIV2L and TTC37. The long-term outcome of this syndrome is still unknown. We aim to describe the long-term outcome, in the French cohort of patients born since 1992. DESIGN: Review of the clinical and biological features of the 15 patients with SD/THE, followed in France and born between 1992 and 2010. RESULTS: All patients presented typical SD/THE syndrome features, of intractable diarrhoea in infancy requiring parenteral nutrition, a facial dysmorphism with hair abnormalities, and immunological disorders. Half of them also had liver and skin abnormalities. Five children died, among which 3 died due to infections. Probabilities of survival according to the Kaplan-Meier method were 93.3%, 86.7%, 74.3 and 61.9%, respectively at 1 year, 5 years, 10 years and 15 years of age. 3/15 were weaned from parenteral nutrition (PN) with likelihood of weaning being 10% at 5 years and 40% at 10 years. At birth 80% were small for gestational age and the short stature persisted in 60%. Haemophagocytic syndrome was noted in 60% and mild mental retardation was present in 60%. CONCLUSIONS: SD/THE is a rare disease with high morbidity and mortality. Management should be focused on nutrition and immunological defects.


Assuntos
Proteínas de Transporte/genética , DNA Helicases/genética , Diarreia Infantil/epidemiologia , Diarreia/genética , Retardo do Crescimento Fetal/epidemiologia , Doenças do Cabelo/epidemiologia , Nutrição Parenteral/estatística & dados numéricos , Distribuição por Idade , Estudos de Coortes , Diarreia Infantil/genética , Diarreia Infantil/imunologia , Facies , Feminino , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/imunologia , França/epidemiologia , Doenças do Cabelo/genética , Doenças do Cabelo/imunologia , Humanos , Lactente , Estimativa de Kaplan-Meier , Fígado/anormalidades , Masculino , Síndrome
17.
Hum Genet ; 133(3): 299-310, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24142340

RESUMO

Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.


Assuntos
Antígenos de Neoplasias/genética , Moléculas de Adesão Celular/genética , Diarreia Infantil/genética , Síndromes de Malabsorção/genética , Glicoproteínas de Membrana/genética , Adolescente , Antígenos de Neoplasias/metabolismo , Sequência de Bases , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Molécula de Adesão da Célula Epitelial , Feminino , Estudos de Associação Genética , Humanos , Imuno-Histoquímica , Lactente , Masculino , Glicoproteínas de Membrana/metabolismo , Mutação , Nutrição Parenteral , Fenótipo , Análise de Sequência de DNA , Resultado do Tratamento
18.
J Pediatr Gastroenterol Nutr ; 52(6): 734-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21478758

RESUMO

BACKGROUND AND OBJECTIVE: Tufting enteropathy (TE) is a congenital abnormality of intestinal mucosa development characterized by severe intestinal failure requiring parenteral nutrition (PN) and, in some cases, small bowel transplantation. A few patients have had a more favorable outcome. The objective of this study was to evaluate possible correlations between histological lesion severity in duodenal biopsies and clinical outcomes in children with TE. PATIENTS AND METHODS: We retrospectively reviewed the records of patients diagnosed with TE between 1993 and 2003 at our institution based on intractable neonatal-onset diarrhea with prolonged dependence on PN and duodenal biopsy findings of villous atrophy, epithelial dysplasia with enterocyte dedifferentiation and disorganization (tufting) of the surface epithelium, and crypt abnormalities. The histological lesions were assessed semiquantitatively and compared with the clinical outcomes including dependence on PN. RESULTS: Seven children, all from consanguineous parents, were studied for a median of 6.5 years. Three were permanently weaned off PN and experienced normal growth without nutritional assistance. Initial biopsies in all 3 children showed severe diffuse histological lesions. At weaning off PN, 2 of these 3 patients had persistent, although less diffuse, histological lesions. CONCLUSIONS: Progressive weaning off PN is possible in some children with TE. In our experience, this favorable outcome was not predicted by histological lesion severity, although the lesions improved in some patients. New biomarkers for identifying the histological lesions and predicting the outcome would be useful.


Assuntos
Diarreia/terapia , Duodeno/patologia , Enteropatias/terapia , Mucosa Intestinal/anormalidades , Mucosa Intestinal/patologia , Nutrição Parenteral , Diarreia/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Enteropatias/complicações , Enteropatias/patologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
19.
Hum Mutat ; 32(3): 277-81, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21120949

RESUMO

The Tricho-Hepato-Enteric (THE) syndrome is an autosomal recessive condition marked by early and intractable diarrhea, hair abnormalities, and immune defects. Mutations in TTC37, which encodes the putative protein Thespin, have recently been associated with THE syndrome. In this article, we extend the pattern of TTC37 mutations by the description of 11 novel mutations in 9 patients with a typical THE syndrome. The mutations were spread along the gene sequence, none of themrecurrent. Different types of mutation were observed: frameshift mutations, splice-site altering mutations, or missense mutations, most of them leading to the creation of a premature stop codon. Concurrently, we investigated the pattern of TTC37 expression in a panel of normal human tissues and showed that this gene is widely expressed, with high levels in vascular tissues, lymph node, pituitary, lung, and intestine. In contrast, TTC37 is not expressed in the liver, an organ that is not consistently affected in THE syndrome. Last, we suggested a model for the putative structure of the unknown Thespin protein.


Assuntos
Proteínas de Transporte/genética , Diarreia/genética , Doenças Genéticas Inatas/genética , Criança , Códon sem Sentido , Feminino , Mutação da Fase de Leitura , Perfilação da Expressão Gênica , Cabelo/anormalidades , Humanos , Síndromes de Imunodeficiência/genética , Masculino , Mutação de Sentido Incorreto , Fenótipo , Isoformas de Proteínas/genética , Síndrome
20.
Biomol Concepts ; 1(1): 41-7, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25961984

RESUMO

Steroids are well-known mediators of many different physiological functions. Their best characterized mechanism of action involves interaction with well-defined nuclear receptors and regulation of gene transcription. However, rapid effects of steroids have been reported which are incompatible with their classical long-term/slow effects. Although the concept of membrane-bound receptors for steroids which can transduce their rapid effects has been proposed many years ago, it is only recently that such proteins have been identified and characterized. In this review, we will discuss recent data regarding the rapid action of progesterone mediated by newly characterized membrane-bound receptors belonging to the progestin and adiponectin receptor family.

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