RESUMO
OBJECTIVE: To assess the contribution of the 113 G-->A missense mutation within the discs, large homolog 5 (DLG5) gene in childhood-onset inflammatory bowel disease (IBD) in Scotland. STUDY DESIGN: Two-hundred and ninety-six children with IBD were studied. Parental DNA was also collected for transmission disequilibrium testing (TDT) analysis. Genotyping was performed by TaqMan. Genotype-phenotype analysis was also undertaken. Socioeconomic status was assigned using a deprivation category (DepCat) score 1 through 7 (1 = most affluent). RESULTS: TDT analysis demonstrated a significant association with IBD (P = .045). On unifactorial analysis, 113A carriage was associated with: (1) higher social class (DepCat 1 compared with 2-7, and 1-2 compared with 3-7) (66.7% vs 22.6%, P = .0005, OR 6.84 [1.99-23.55] and 37.2% vs 22.2%, P = .03, OR 2.08 [1.04-4.17], respectively); (2) higher height centile (>75th centile vs <75th centile) (42.9% vs 23.1%, P = .01, OR 2.50 [1.18-5.28]); and (3) male sex in Crohn's disease (CD) (29.3% vs 16.9%, P = .04, OR 2.04 [1.01-4.11]). Multifactorial analysis demonstrated that higher social class (DepCat 1) was independently associated with carriage of variants of 113A (P = .001, OR = 6.92 [2.24-21.33]). CONCLUSIONS: DLG5 113A is associated with increased susceptibility to IBD in Scottish children. The effect may be most marked for those children living in relative affluence.
Assuntos
Predisposição Genética para Doença/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Proteínas de Membrana/genética , Mutação de Sentido Incorreto , Proteínas Supressoras de Tumor/genética , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Regulação da Expressão Gênica , Heterozigoto , Humanos , Incidência , Doenças Inflamatórias Intestinais/fisiopatologia , Modelos Logísticos , Masculino , Razão de Chances , Linhagem , Fenótipo , Probabilidade , Prognóstico , Escócia/epidemiologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.
Assuntos
Biomarcadores , Fibrose Cística/complicações , Deficiência de Vitamina K/tratamento farmacológico , Vitaminas/administração & dosagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Precursores de Proteínas/sangue , Protrombina , Tempo de Protrombina , Vitamina K/administração & dosagem , Deficiência de Vitamina K/complicaçõesRESUMO
A 3-year-old girl presented with hemolytic anemia, hepatosplenomegaly, ascites, and evidence of decompensated chronic liver disease. Genotypic DNA analysis revealed that the patient was homozygous for a splice site mutation now designated IVS4-1:G>C, expected to destroy completely the functional gene product of ATP7B, the gene responsible for Wilson's disease. We suggest that this severe mutation caused very early liver disease. Wilson's disease should be considered in the differential diagnosis of established liver disease in the preschool-aged child.
Assuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte/genética , Proteínas de Transporte de Cátions , Degeneração Hepatolenticular/diagnóstico , Criança , Pré-Escolar , ATPases Transportadoras de Cobre , Diagnóstico Diferencial , Feminino , Degeneração Hepatolenticular/genética , Humanos , MutaçãoRESUMO
The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.