ABSTRACT
Wilson disease [WD] is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase [ATPase] encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation [p.H1069Q] in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group. Direct DNA sequencing was applied to exons [13, 14, 18, and 19] of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families [three families]. We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution [p.A1074A] in 16% of patients and the other was predicted to be missense disease-causing mutations [p.T1076I] in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients. Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations
ABSTRACT
To study the prevalence of metabolic syndrome [MS], insulin resistance [IR] and non-alcoholic fatty liver disease [NAFLD] in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase [ALT]. Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c] and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Twenty patients [60.6%] were labeled with MS. IR was present in 16 [48.4%]. Fifteen [44%] patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy [P=0.001]. Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology [P<0.05] and fitted more with the criteria of MS [80% vs. 44%]. IR was significantly more common among NAFLD patients [73% vs. 28%]. There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD