Gene mutations in Wilson disease in Egyptian children: report on two novel mutations

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

Outpatient blind percutaneous liver biopsy in infants and children: is it safe?

We aim to investigate the safety of outpatient blind percutaneous liver biopsy [BPLB] in infants and children with chronic liver disease [CLD]. BPLB was performed as an outpatient procedure using the aspiration Menghini technique in 80 infants and children, aged 2 months to 14 yrs, for diagnosis of their CLD. Patients were divided into three groups: Group 1 [<1 year], group 2 [1-6 yrs], and group 3 [6-14 yrs]. The vital signs were closely monitored 1 hr before biopsy, and then 1, 2, 6, and 24 hrs after biopsy. Twenty-four hours pre-and post-biopsy complete blood counts, liver enzymes, prothrombin time [PT], and abdominal ultrasonography, searching for a biopsy-induced hematoma, were done for all patients. No mortality or major morbidities were encountered after BPLB. The rate of minor complications was 17.5% including irritability or "pain" requiring analgesia in 10%, mild fever in 5%, and drowsiness for>6 hrs due to oversedation in 2.5%. There was a statistically significant rise in the 1-hr post-biopsy mean heart and respiratory rates, but the rise was non-significant at 6 and 24 hrs except for group 2 where heart rate and respiratory rates significantly dropped at 24 hrs. No statistically significant difference was noted between the mean pre-biopsy and the 1, 6, and 24-hrs post-biopsy values of blood pressure in all groups. The 24-hrs post-biopsy mean hemoglobin and hematocrit showed a significant decrease, while the 24-hrs post-biopsy mean total leucocyte and platelet counts showed non-significant changes. The 24-hrs post-biopsy mean liver enzymes were non-significantly changed except the 24-hrs post-biopsy mean PT which was found to be significantly prolonged, for a yet unknown reason[s]. Outpatient BPLB performed by the Menghini technique is safe and well tolerated even in infants and young children. Frequent, close monitoring of patients is strongly recommended to achieve optimal patient safety and avoid potential complications

association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children

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

Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: single center study

Pediatric non-alcoholic fatty liver disease [NAFLD] is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. Seventy-six children [2-15 years] were included after an informed consent. All were subjected to full anthropometric assessment [including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio], biochemical assessment of liver function tests, lipid profile and insulin: Sixteen patients [21%] had elevated ALT and 6 [7.9%] had elevated AST. Significant dyslipidemia [low HDL-c, high total cholesterol, high LDL-c and triglycerides] and higher insulin resistance were found in obese patients [P<0.01]. The main sonographic findings were hepatomegaly in 20 patients [26.3%] and echogenic liver in 41 patients [53.9%]. Liver biopsy showed simple steatosis in eight cases [24.2%] and non-alcoholic steatohepatitis [NASH] in seven cases [21.2%]. Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor [independent variable] for NAFLD in both uni- and multivariate logistic regression analyses. Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children

Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children

Polymorphisms in the promoter of microsomal triglyceride transfer protein [MTP] lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis [NASH]. The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction [PCR] and restriction fragment length polymorphism for the -493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase [MnSOD]. Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype [P = 0.002, CI: 2.9-392] compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype

Evaluation of TC sign by 3 dimensional sonography in extrahepatic biliary atresia: a prospective study

The tubular or triangular cord sign [TC sign] is very sensitive and specific in diagnosis of extrahepatic biliary atresia. It is a b and -like periportal echogenicity, which represents a cone shaped fibrotic mass cranial to the bifurcation of portal vein. TC sign anatomic characterization using 3 dimensional sonography in infants with biliary atresia. 20 infants having biliary atresia underwent both 2 dimensional and 3 dimensional ultrasonographic examinations using both 5 and 7 MHz convex linear transducers. Ultrasonographic findings were correlated to intraoperative details. 11 infants with neonatal hepatitis with absent TC sign were evaluated as a control group. The TC sign identified on 2 dimensional sonography was identified by 3 dimensional sonography. 3D ultra-sonography characterized the TC sign as the left hepatic bile duct, which was completely obliterated in 18 infants, [confirmed by intra-operative findings] and partially occluded in 2. It converged to meet the right hepatic duct which was also seen occluded [in all cases] as a fibrotic b and seen through a right modified oblique lateral scan [while using the liver as an acoustic window]. The common hepatic duct was seen occluded in all infants. The common bile duct was seen occluded in all except one which showed non-communicating cystic dilatation [confirmed by intra-operative cholangiogra-phy]. All infants with idiopathic neonatal hepatitis had patent intact biliary systems and recovered in the following 6-10 months. TC sign represents the obliterated left hepatic bile duct. 3Dimensional ultrasonography is superior to 2D sonography in providing better diagnostic imaging of the biliary tract in infants with cholestasis