Mutations of ATP7B gene in two Thai siblings with Wilson disease

Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B gene. Objective: Report the clinical data and mutation analysis of two Thai siblings suspected of WD. Subject and methods: A 13-year-old boy who presented with cirrhosis, arthralgia, hypoalbuminemia, and coagulopathy, and his 11-year-old sister who was asymptomatic but had hepatomegaly with elevation of transaminases, were studied. Mutation analysis of ATP7B gene and mRNA analysis was performed in both patients and their parents. Results: Investigations were consistent with WD, and their liver diseases improved after standard treatment for WD. DNA analyses in these two patients revealed two novel mutations, which were a deletion of the first 2bp of exon 6 (c.1870_1871delGA), and a single base substitution from A to G at nucleotide 4075 (c.4075A>G) in the exon 20 (p.M1359V). PCR-restriction digestion with NcoI restriction enzyme was employed as the second method for confirmation of the c.4075A>G mutation and for rapid screening in 100 chromosomes from unrelated healthy controls, and this variant was not present in the controls. The c.1870_1871delGA deletion caused a frameshift effect, which results in a premature stop codon (p.E624fsX753), and the p.M1359V mutation is a substitution of methionine with valine, which may have effects upon its orientation and interaction with other adjacent amino acids. Conclusion: Two novel mutations of ATP7B gene were identified in two Thai siblings with WD.

Extramedullary haematopoietic tumor producing small intestinal intussusception in a beta-thalassemia/hemoglobin E Thai boy: a case report.

The authors report a case of beta-thalassemia/hemoglobin E disease with extramedullary haematopoietic tumor which developed at the small intestine and caused intussusception. A 7 year-old boy with homozygous beta-thalassemia/hemoglobin E presented with recurrent abdominal pain. The abdominal ultrasonography showed ileo-ileal intussusception with a solid mass as the leading point. Resection of the ileal segment was performed. Pathological examination revealed an extramedullary haematopoietic tumor forming an intraluminal polypoid mass, being the leading point of the intussusception. Extramedullary haematopoiesis in the intestinal tract is rare. To our knowledge, this is the first case of extramedullary haematopoietic tumor that produced intussusception of the small intestine in a beta-thalassemia/hemoglobin E patient.

The role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in pathogenesis of dengue hemorrhagic fever (DHF).

In previous studies it has been demonstrated that the levels of plasma 6 keto-prostaglandin F1 alpha (6-K-PGF1), the stable metabolite of PGI2 were elevated in DHF patients during shock. In this study it is hypothesized that excessive PGI2 production plays a very important role in developing serious clinical manifestations of dengue shock syndrome (DSS) patients. In addition, an attempt was made to determine whether TXA2 has any significant role in such patients. Plasma 6-K-PGF1 and thromboxane B2 (TXB2), the stable metabolites of TXA2 were determined in 43 normal healthy children (NC) and 54 DHF patients without shock (DHF-N) and 33 DHF patients with shock (DHF-S). Subjects aged between 2 and 14 years. Plasma 6-K-PGF1 and TXB2 were measured by radioimmunoassay and the ratio of TXB2/6-K-PGF1 were also calculated. In 43 NC the values of plasma TXB2, 6-K-PGF1 and TXB2/6-K-PGF1 ratio were (mean +/- SE) 372.3 +/- 17.1, 150.1 +/- 2.4 and 2.52 +/- 0.12 pg/ml, respectively. In 54 DHF-N patients the corresponding values were 409.1 +/- 16.0, 278.4 +/- 11.6 and 1.54 +/- 0.06 pg/ml; whereas those in 33 DHF-S patients were 254.3 +/- 26.2, 349.1 +/- 20.5 and 0.757 +/- 0.073 pg/ml, respectively. Plasma 6-K-PGF1 levels of DHF-N and DHF-S patients were significantly greater than those in normal children (p < 0.001, p < 0.01 respectively). The plasma 6-K-PGF1 levels seem to be greater in DHF-S patients than in the DHF-N patients, however the difference in values were not statistically significant (p > 0.05). These findings indicate that plasma PGI2 level is significantly increased in DHF particularly during shock. Plasma TXB2 levels of DHF-N had no significant statistical difference from those of NC (p > 0.05); however, those in DHF-S patients were significantly lowered (p < 0.001) than those of NC and DHF-N patients. The findings suggest the important role of TXA2 to compensate for excessive PGI2 secretion in DHF patients. The failure or inadequate TXA2 production may eventually lead to shock. The ratios were significantly reduced in both DHF-N and DHF-S patients when compared to those of NC (p < 0.001 both). The ratio in DHF-S patients was also significantly lowered than that in DHF-N patients (p < 0.001). It is suggested that the imbalance between TXA2 and PGI2 production exists during DHF infection. The more reduction of plasma TXA2/PGI2 ratio leads to more overt and serious clinical manifestations of the disease.